The Journal of Organic Chemistry
Note
1g was obtained as a colorless oil (175.2 mg, 49%): 1H NMR
(360 MHz, CDCl3) δ 8.16 (dt, J = 8.8, 2.2 Hz, 2H), 7.42 (dt, J = 8.1,
2.6 Hz, 2H), 2.65 (d, J = 7.0 Hz, 2H), 1.06−0.95 (m, 1H), 0.62−0.57
(m, 2H), 0.27−0.23 (m, 2H); 13C NMR (90 MHz, CDCl3) δ 150.2,
146.6, 129.2 (2C), 123.7 (2C), 40.3, 11.5, 5.0 (2C); HRMS (EI) calcd
for C10H11NO2 [(M+.)] 177.0790, found 177.0803; IR (neat) ν 3079,
2933, 1599, 1516, 1344 cm−1.
(EI) calcd for C16H18O2 [(M+.)] 242.1307, found 242.1288; IR
(neat) ν 2958, 2906, 1612, 1513, 1247, 1096 cm−1.
{[4-(2-Phenylethoxy)butoxy]methyl}benzene (2b). Following
standard procedure B, the reaction was performed starting from
potassium (4-methoxy)benzyloxymethyltrifluoroborate (900.5 mg,
3.0 mmol). After 24 h, the resulting crude was purified by preparative
plate chromatography (heptanes/EtOAc 70:30); 2b was obtained as a
1
1-Cyclopropylmethyl-3-nitrobenzene (1h). Following standard
procedure A, the reaction was performed starting from 3-nitrobenzyl
chloride (353.8 mg, 2.0 mmol). After 7 h, the resulting crude was
purified by preparative plate chromatography (heptane/EtOAc 85:15);
colorless oil (302.4 mg, 62%): H NMR (360 MHz, CDCl3) δ 7.37−
7.18 (m, 10H), 4.49 (s, 2H), 3.62 (t, J = 7.1 Hz, 2H), 3.49−3.44
(m, 4H), 2.88 (t, J = 7.3 Hz, 2H), 1.68−1.65 (m, 4H); 13C NMR (90
MHz, CDCl3) δ 139.1, 138.7, 128.9 (2C), 128.3 (2C), 128.3 (2C),
127.6 (2C), 127.5, 126.1, 72.8, 71.8, 70.7, 70.1, 36.4, 28.5; HRMS (EI)
calcd for C19H25O2 [(M+.)] 285.1855, found 285.1839; IR (neat) ν
2932, 2858, 1454, 1363, 1102 cm−1.
1
1h was obtained as a colorless oil (281.9 mg, 80%): H NMR (360
MHz, CDCl3) δ 8.14 (s, 1H), 8.07 (br d, J = 8.4 Hz, 1H), 7.60 (d, J =
7.3 Hz, 1H), 7.46 (t, J = 7.9 Hz, 1H), 2.65 (d, J = 7.0 Hz, 2H), 1.07−
0.96 (m, 1H), 0.61−0.58 (m, 2H), 0.27−0.23 (m, 2H); 13C NMR
(90 MHz, CDCl3) δ 148.4, 144.3, 134.7, 129.2, 123.2, 121.2, 34.0,
11.5, 4.9 (2C); HRMS (EI) calcd for C10H11NO2 [(M+.)] 177.0790,
found 177.0767; IR (neat) ν 3078, 3002, 1524, 1349, 806 cm−1.
Methyl 4-Cyclopropylmethylbenzoate (1j). Following standard
procedure A, the reaction was performed starting from methyl 4-
(chloromethyl)benzoate (380.7 mg, 2.0 mmol). After 4 h, the resulting
crude was purified by preparative plate chromatography (heptane/
EtOAc 70:30); 1j was obtained as a colorless oil (278.2 mg, 73%).1H
NMR (360 MHz, CDCl3) δ 7.97 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4
Hz, 2H), 3.90 (s, 3H), 2.6 (d, J = 7.0 Hz, 2H), 1.05−0.94 (m, 1H),
0.57−0.52 (m, 2H), 0.24−0.20 (m, 2H); 13C NMR (90 MHz, CDCl3)
δ 167.2, 147.7, 129.7 (2C), 128.4 (2C), 127.9, 52.0, 40.3, 11.6, 4.8
(2C); HRMS (EI) calcd for C12H14O2 [(M+.)] 190.0994, found
190.0981; IR (neat) ν 3001, 1719, 1434, 1277, 1108 cm−1.
4-(2-Phenethyloxyethyl)-morpholine (2c). Following standard
procedure B, the reaction was performed starting from potassium
[2-(morpholin-4-yl)ethoxy]methyltrifluoroborate (792.9 mg, 3.0
mmol). After 24 h, the resulting crude was purified by preparative
plate chromatography [CH2Cl2/ammonia (7 M in MeOH)/heptanes
60:2:38]; 2c was obtained as a colorless oil (211.5 mg, 45%): 1H NMR
(360 MHz, CDCl3) δ 7.28 (t, J = 7.3 Hz, 2H), 7.22−7.18 (m, 3H),
3.70−3.64 (m, 6H), 3.59 (t, J = 5.7 Hz, 2H), 2.88 (t, J = 7.1 Hz, 2H),
2.57 (t, J = 5.5 Hz, 2H), 2.46−2.45 (m, 4H); 13C NMR (90 MHz,
CDCl3) δ 139.0, 129.0 (2C), 128.4 (2C), 126.3, 72.2, 68.5, 66.9 (2C),
58.3, 54.1 (2C), 36.3; HRMS (EI) calcd for C14H21NO2 [(M+.)]
235.1572, found 235.1577; IR (neat) ν 2854, 1453, 1115, 699 cm−1.
Trimethyl-(2-phenethyloxyethyl)silane (2d). Following standard
procedure B, the reaction was performed starting from (2-
trimethylsilyl)-ethoxymethyl trifluoroborate (752.1 mg, 3.0 mmol).
After 5 days, the resulting crude was purified by preparative plate
chromatography (heptanes/EtOAc 70:30); 2d was obtained as a
yellow oil (198.6 mg, 45%): 1H NMR (360 MHz, CDCl3) δ 7.32−7.19
(m, 5H), 3.64 (t, J = 7.3 Hz, 2H), 3.55−3.51 (m, 2H), 2.94−2.88 (m, 2H),
0.98−0.93 (m, 2H), 0.01 (s, 9H); 13C NMR (90 MHz, CDCl3) δ
139.3, 129.0 (2C), 128.5 (2C), 126.3, 71.4, 68.2, 36.6, 18.3, −1.2
4-Cyclopropylmethyl-benzonitrile (1k). Following standard proce-
dure A, the reaction was performed starting from 4-chloromethylben-
zonitrile (309.4 mg, 2.0 mmol). After 3 h, the resulting crude was
purified by preparative plate chromatography (heptane/EtOAc 80:20);
1
1k was obtained as a colorless oil (186.8 mg, 59%): H NMR (360
MHz, CDCl3) δ 7.59 (dt, J = 8.1, 1.8 Hz, 2H), 7.37 (d, J = 8.1 Hz,
2H), 2.61 (d, J = 7.0 Hz, 2H), 1.03−0.93 (m, 1H), 0.61−0.56 (m,
2H), 0.24−0.20 (m, 2H); 13C NMR (90 MHz, CDCl3) δ 148.0, 132.2
(2C), 129.2 (2C), 119.3, 109.9, 40.5, 11.4, 4.9 (2C); HRMS (EI) calcd
for C11H11N [(M+.)] 157.0897, found 157.0918; IR (neat) ν 3079,
3003, 2227, 1608, 1020, 826 cm−1.
+
(3C); HRMS (CI) calcd for C13H26NOSi [(MNH4 )] 240.1784,
found 240.1765; IR (neat) ν 2951, 2855, 1248, 1102, 835 cm−1.
(2-Cyclopentyloxyethyl)benzene (2e). Following standard proce-
dure B, the reaction was performed starting from potassium cyclo-
pentoxymethyltrifluoroborate (650.7 mg, 3.0 mmol). After 24 h, the
resulting crude was purified by preparative plate chromatography
(heptanes/EtOAc 70:30); 2e was obtained as a colorless oil (153.0
mg, 40%): 1H NMR (360 MHz, CDCl3) δ 7.31−7.18 (m, 5H), 3.93−
3.88 (m, 1H), 3.58 (t, J = 7.3 Hz, 2H), 2.87 (t, J = 7.5 Hz, 2H), 1.73−
1.48 (m, 8H); 13C NMR (90 MHz, CDCl3) δ 139.4, 129.1 (2C), 128.4
(2C), 126.2, 81.6, 70.0, 36.9, 32.4 (2C), 23.6 (2C); HRMS (EI) calcd
for C13H16 [(M+. − H2O)] 172.1252, found 172.1274; IR (neat) ν
2954, 2777, 1736, 1349, 1093 cm−1.
1-Chloro-4-cyclopropylmethylbenzene (1l). Following standard
procedure A, the reaction was performed starting from 4-chloro-benzyl
chloride (332.1 mg, 2.0 mmol). After 10 h, the resulting crude was
purified by preparative plate chromatography (heptanes/EtOAc 95:5);
1
1l was obtained as a colorless oil (112.9 mg, 34%): H NMR (360
MHz, CDCl3) δ 7.07 (dt, J = 8.4, 1.8 Hz, 2H), 7.00 (dt, J = 8.1, 1.8 Hz,
2H), 2.51 (d, J = 7.0 Hz, 2H), 1.00−0.89 (m, 1H), 0.55−0.50 (m, 2H),
0.21−0.17 (m, 2H); 13C NMR (90 MHz, CDCl3) δ 140.7, 131.6, 129.8
(2C), 128.4 (2C), 39.8, 11.9, 4.8 (2C); HRMS (EI) calcd for C10H11Cl
[(M+.)] 166.0549, found 166.0524; IR (neat) ν 3002, 2918, 1491, 1088,
1016 cm−1.
tert-Butyl 4-(2-Phenylethoxy)piperidine-1-carboxylate (2f). Fol-
lowing standard procedure B, the reaction was performed starting from
potassium (1-Boc-4-piperidinylmethoxyoxy)methyltrifluoroborate
(1.01 g, 3.0 mmol). After 24 h, the resulting crude was purified by
preparative plate chromatography (CH2Cl2/heptane/ammonia
60:37:3); 2f was obtained as a yellow oil (253.9 mg, 42%): 1H
NMR (360 MHz, CDCl3) δ 7.31−7.19 (m, 5H), 3.71−3.64 (m, 4H),
3.10 (sept, J = 3.7 Hz, 1H), 3.07 (ddd, J = 13.1, 9.2, 3.3 Hz, 2H), 2.88
(t, J = 7.3 Hz, 2H), 1.81−1.53 (br m, 2H), 1.54−1.46 (m, 2H), 1.45
(s, 9H); 13C NMR (90 MHz, CDCl3) δ 155.0, 139.2, 129.1 (2C),
128.4 (2C), 126.3, 79.5, 77.4, 74.7, 69.2, 41.2, 36.9, 31.0, 28.6 (3C);
HRMS (EI) calcd for C14H18NO3 [(M+. − C4H9)] 248.1287, found
248.1290; IR (neat) ν 2929, 2861, 1690, 1420, 1169, 1028 cm−1.
(2-tert-Butoxy-ethyl)-benzene (2g). Following standard procedure
B, the reaction was performed starting from potassium tert-
butoxymethyltrifluoroborate (612.8 mg, 3.0 mmol). After 24 h, the
resulting crude was purified by preparative plate chromatography
(heptanes/EtOAc 95:5); 2g was obtained as a colorless oil (104.0 mg,
29%): 1H NMR (360 MHz, CDCl3) δ 7.31−7.19 (m, 5H), 3.54 (t, J =
7.7 Hz, 2H), 2.83 (t, J = 7.7 Hz, 2H), 1.18 (s, 9H); 13C NMR (90 MHz,
CDCl3) δ 139.5, 129.1 (2C), 128.4 (2C), 126.2, 73.0, 63.2, 37.6, 27.7
Procedure B. 1-Methoxy-4-phenethyloxymethylbenzene (2a).
A Biotage microwave vial was charged with benzyl chloride
(255.7 mg, 2.0 mmol), potassium (4-methoxy)benzyltrifluoroborate
(900.5 mg, 3.0 mmol), PEPPSI (69.5 mg, 0.1 mmol), and
K2CO3 (552.8 mg, 4.0 mmol). The tube was sealed and purged
with nitrogen. A degassed mixture of toluene/H2O 19:1
(mL/mL) was added under a nitrogen atmosphere. The re-
action was stirred at 120 °C for 24 h. After cooling to room
temperature, the reaction mixture was filtered through Celite
and MgSO4. The solvent was removed in vacuo, and the residue
was purified by preparative plate chromatography (silica gel,
heptanes/EtOAc 70:30) to obtain 2a as a colorless oil (377.1
mg, 66%): The spectral data match those reported in the
literature;33 1H NMR (360 MHz, CDCl3) δ 7.31−7.18 (m, 7H),
6.86 (dt, J = 8.4, 2.6 Hz, 2H), 4.46 (s, 2H), 3.80 (s, 3H), 3.66
(t, J = 7.3 Hz, 2H), 2.92 (t, J = 7.1 Hz, 2H); 13C NMR
(90 MHz, CDCl3) δ 159.2, 139.1, 130.6, 129.2 (2C), 129.0
(2C), 128.4 (2C), 126.2, 113.8 (2C), 72.6, 71.0, 55.2, 36.4; HRMS
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dx.doi.org/10.1021/jo202686p | J. Org. Chem. 2012, 77, 2966−2970