J. Lee et al. / Bioorg. Med. Chem. 14 (2006) 2022–2031
2029
was purified by flash chromatography using EtOAc–
hexanes = 1:2 to afford 6.
0.22 mmol) and stirred for 30 min. The reaction mixture
was diluted with H2O and then extracted with
EtOAc several times. The combined organic layers were
concentrated in vacuo and the residue was purified by
flash chromatography using EtOAc–hexanes = 1:4 to
afford 7.
5.1.6.1. 3-Hydroxy-2-(2-hydroxybenzyl)propyl pivalate
1
(6a). 85% yield, white solid, mp = 61–62 ꢁC: H NMR
(CDCl3) d 7.04–7.15 (m, 2H), 6.83 (m, 2H), 4.12 (ddd of
AB, 2H, 2· CH2OCO), 3.50 (ddd of AB, 2H, 2· CH2OH),
2.70 (ddd of AB, 2H, ArCH2CH), 2.10 (m, 1H,
ArCH2CH), 1.21 (s, 9H, C(CH3)3); IR (neat) 3395
(OH), 1704 (C@O); MS (FAB) m/z 267 (MH+); Anal.
Calcd for C15H22O4: C, 67.64; H, 8.33. Found: C, 67.86;
H, 8.36.
5.1.7.1. 2-[2-(Hexanoyloxy)benzyl]-3-hydroxypropyl
pivalate (7a). 91% yield, colorless oil: 1H NMR (CDCl3)
d 7.15–7.3 (m, 3H, Ar), 7.03 (m, 1H, Ar), 4.20 (dd, 1H,
CH2OCO), 4.07 (dd, 1H, CH2OCO), 3.54 (dd, 1H,
CH2OH), 3.44 (dd, 1H, CH2OH), 2.5–2.65 (m, 4H,
ArCH2CH and COCH2), 2.15 (m, 1H, ArCH2CH),
1.7–1.8 (m, 2H, COCH2CH2), 1.35–1.45 (m, 4H,
(CH2)2CH3), 1.22 (s, 9H, C(CH3)3), 0.93 (distorted t,
3H, CH3); IR (neat) 3443 (OH), 1758, 1727 (C@O);
MS (FAB) m/z 365 (MH+); Anal. Calcd for C21H32O5:
C, 69.20; H, 8.85. Found: C, 69.40; H, 8.87.
5.1.6.2. 3-Hydroxy-2-(3-hydroxybenzyl)propyl pivalate
1
(6b). 88% yield, white solid, mp = 95–96 ꢁC: H NMR
(CDCl3) d 7.16 (t, 1H), 6.65–6.77 (m, 2H), 5.18 (br s,
1H, OH), 4.10 (ddd of AB, 2H, 2· CH2OCO), 3.53 (ddd
of AB, 2H, 2· CH2OH), 2.60 (ddd of AB, 2H,
ArCH2CH), 2.11 (m, 1H, ArCH2CH), 1.23 (s, 9H,
C(CH3)3); IR (neat) 3396 (OH), 1704 (C@O); MS
(FAB) m/z 267 (MH+); Anal. Calcd for C15H22O4: C,
67.64; H, 8.33. Found: C, 67.88; H, 8.35.
5.1.7.2. 2-[3-(Hexanoyloxy)benzyl]-3-hydroxypropyl
pivalate (7b). 93% yield, colorless oil: 1H NMR (CDCl3)
d 7.30 (dt, 1H, Ar), 7.05 (br d, 1H, Ar), 6.9–6.96 (m, 2H,
Ar), 4.21 (dd, 1H, CH2OCO), 4.06 (dd, 1H, CH2OCO),
3.58 (dd, 1H, CH2OH), 3.46 (dd, 1H, CH2OH), 2.66
(ddd of AB, 2H, ArCH2CH), 2.54 (t, 2H, COCH2),
2.11 (m, 1H, ArCH2CH), 1.7–1.8 (m, 2H, COCH2CH2),
1.3–1.45 (m, 4H, (CH2)2CH3), 1.23 (s, 9H, C(CH3)3),
0.94 (distorted t, 3H, CH3); IR (neat) 3440 (OH),
1760, 1728 (C@O); MS (FAB) m/z 365 (MH+); Anal.
Calcd for C21H32O5: C, 69.20; H, 8.85. Found: C,
69.42; H, 8.88.
5.1.6.3. 3-Hydroxy-2-(2-hydroxybenzyl)propyl pivalate
(6c). 90% yield, colorless oil: 1H NMR (CDCl3) d 7.02 (d,
2H), 6.74 (d, 2H), 5.2 (br s, 1H, OH), 4.12 (ddd of AB, 2H,
2· CH2OCO), 3.50 (ddd of AB, 2H, 2· CH2OH), 2.56
(ddd of AB, 2H, ArCH2CH), 2.06 (m, 1H, ArCH2CH),
1.21 (s, 9H, C(CH3)3); IR (neat) 3398 (OH), 1704
(C@O); MS (FAB) m/z 267 (MH+); Anal. Calcd for
C15H22O4: C, 67.64; H, 8.33. Found: C, 67.89; H, 8.37.
5.1.6.4. 2-(2-Hydroxyphenyl)-3-hydroxypropyl pivalate
(14a). 92% yield, colorless oil: H NMR (CDCl3) d 8.24
5.1.7.3. 2-[4-(Hexanoyloxy)benzyl]-3-hydroxypropyl
pivalate (7c). 92% yield, colorless oil: 1H NMR (CDCl3)
d 7.19 (d, 2H, Ar), 7.00 (d, 2H, Ar), 4.21 (dd, 1H, CH2O-
CO), 4.05 (dd, 1H, CH2OCO), 3.58 (dd, 1H, CH2OH),
3.46 (dd, 1H, CH2OH), 2.64 (ddd of AB, 2H,
ArCH2CH), 2.54 (t, 2H, COCH2), 2.10 (m, 1H,
ArCH2CH), 1.7–1.8 (m, 2H, COCH2CH2), 1.35–1.45
(m, 4H, (CH2)2CH3), 1.23 (s, 9H, C(CH3)3), 0.94 (dis-
torted t, 3H, CH3); IR (neat) 3447 (OH), 1760, 1728
(C@O); MS (FAB) m/z 365 (MH+); Anal. Calcd for
C21H32O5: C, 69.20; H, 8.85. Found: C, 69.44; H, 8.88.
1
(br s, 1H, OH), 7.05–7.2 (m, 2H), 6.8–6.9 (m, 2H), 4.65
(dd of AB, 1H, CH2OCO), 4.25 (dd of AB, 1H, CH2O-
CO), 3.95 (ddd of AB, 2H, CH2OH), 3.26 (m, 1H, ArCH),
1.19 (s, 9H, C(CH3)3); IR (neat) 3395 (OH), 1704 (C@O)
cmÀ1; MS (FAB) m/z 275 (MNa+); Anal. Calcd for
C14H20O4: C, 66.65; H, 7.99. Found: C, 66.90; H, 8.01.
5.1.6.5. 2-(3-Hydroxyphenyl)-3-hydroxypropyl pivalate
1
(14b). 93% yield, colorless oil: H NMR (CDCl3) d 7.17
(m, 1H), 6.7–6.8 (m, 3H), 6.47 (br s, 1H, OH), 4.34 (ddd
of AB, 2H, CH2OCO), 3.82 (d of AB, 2H, CH2OH),
3.11 (m, 1H, ArCH), 2.51 (br s, 1H, OH), 1.15 (s, 9H,
C(CH3)3); IR (neat) 3395 (OH), 1706 (C@O) cmÀ1; MS
(EI) m/z 252 (M+); Anal. Calcd for C14H20O4: C, 66.65;
H, 7.99. Found: C, 66.88; H, 8.02.
5.1.7.4. 2-[2-(Hexanoyloxy)phenyl]-3-hydroxypropyl
pivalate (15a). 90% yield, colorless oil: 1H NMR
(CDCl3) d 7.2–7.4 (m, 3H), 7.04 (m, 1H), 4.34 (ddd of
AB, 2H, CH2OCO), 3.81 (ddd of AB, 2H, CH2OH),
3.34 (m, 1H, ArCH), 2.60 (t, 2H, COCH2), 2.32 (dt,
1H, OH), 1.7–1.8 (m, 2H, COCH2CH2), 1.3–1.45 (m,
4H, (CH2)2CH3), 1.16 (s, 9H, C(CH3)3), 0.93 (distorted
t, 3H, CH3); IR (neat) 3524, 1760, 1730 cmÀ1; MS
(FAB) m/z 373 (MNa+); Anal. Calcd for C20H30O5: C,
68.54; H, 8.63. Found: C, 68.78; H, 8.66.
5.1.6.6. 2-(4-Hydroxyphenyl)-3-hydroxypropyl pivalate
(14c). 94% yield, white solid, mp = 123–124 ꢁC: 1H NMR
(CDCl3) d 7.09 (dt, 2H, Ar), 6.77 (dt, 2H, Ar), 5.81 (br s,
1H, OH), 4.32 (ddd of AB, 2H, CH2OCO), 3.82 (ddd of
AB, 2H, CH2OH), 3.11 (m, 1H, ArCH), 2.05 (br s, 1H,
OH), 1.17 (s, 9H, C(CH3)3); IR (neat) 3169 (OH), 1723
(C@O) cmÀ1; MS (FAB) m/z 253 (MH+); Anal. Calcd
for C14H20O4: C, 66.65; H, 7.99. Found: C, 66.92; H, 8.00.
5.1.7.5. 2-[3-(Hexanoyloxy)phenyl]-3-hydroxypropyl
pivalate (15b). 89% yield, colorless oil: 1H NMR
(CDCl3) d 7.34 (m, 1H), 7.13 (m, 1H), 6.96–7.02 (m,
2H), 4.38 (ddd of AB, 2H, CH2OCO), 3.84 (d, 2H,
CH2OH), 3.17 (m, 1H, ArCH), 2.55 (t, 2H, COCH2),
2.34 (t, 1H, OH), 1.7–1.8 (m, 2H, COCH2CH2), 1.3–
1.45 (m, 4H, (CH2)2CH3), 1.16 (s, 9H, C(CH3)3), 0.93
(distorted t, 3H, CH3); IR (neat) 3524, 1760,
5.1.7. General procedure for hexanoylation. A cooled
solution of 6 (48 mg, 0.18 mmol) and a catalytic amount
of 4-dimethylaminopyridine in CH2Cl2 (2 mL) at 0 ꢁC
was treated with n-hexanoic anhydride (0.05 mL,