NMR (400 MHz, DMSO-d
6
) δ 1.41 (9H, s), 2.40-2.46 (2H, m), 3.57 (2H, t, J = 5.6 Hz), 4.29 (2H, s), 6.79
+
(
2H, s). MS (EI) m/z 255 (M ). Anal. Calcd for C11
H
17
N O
3 2
S·0.1H
2
O: C, 51.38; H, 6.74; N, 16.34; S,
1
2.47. Found: C, 51.73; H, 6.96; N, 16.44; S, 12.14.
-Bromo-5-tert-butoxycarbonyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (19)
(181 g, 0.808 mol) in dry DMF (500 mL) was added tert-butyl nitrite
104 g, 1.01 mol). To the stirred mixture at 50 °C was added 18 (172 g, 0.674 mol) in portions. The
reaction mixture was stirred at 50-60 °C for 2 h and concentrated in vacuo. Purification of the residue by
2
To a stirred suspension of CuBr
2
(
2
column chromatography (hexane/AcOEt, 5/1) and crystallization from Et O gave 19 (105 g, 49%) as a
1
colorless solid: mp 42-44 °C. H NMR (400 MHz, CDCl
3
) δ 1.48 (9H, s), 2.85 (2H, br s), 3.72 (2H, t, J =
+
79
+
81
5
.6 Hz), 4.56 (2H, br s). MS (FAB) m/z 319 [(M + H) , Br ], 321 [(M + H) , Br ]. Anal. Calcd for
BrS: C, 41.39; H, 4.74; N, 8.78; Br, 25.03; S, 10.05. Found: C, 41.33; H, 4.68; N, 8.77; Br,
11 15 2
C H N
2
5.21; S, 10.15.
2
-Bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (20)
To a stirred solution of 19 (74.7 g, 234 mmol) in CH Cl (160 mL) was added trifluoroacetic acid (500 g)
2
2
at 0 °C in an ice bath. The mixture was stirred at rt for 10 min and concentrated in vacuo. To the residue
was added Et O (300 mL) to obtain a colorless solid. To the suspension of this solid in CH Cl (150 mL)
was added Et N (63.7 mL, 460 mmol). To the stirred mixture at rt were added AcOH (39.4 mL, 689
2
2
2
3
mmol), 36 % aq. HCHO (39.4 mL), and sodium triacetoxyborohydride (80.3 g, 367 mmol). The mixture
was stirred for 1 h at rt under an argon atmosphere and poured into 1N NaOH (750 mL). The organic
layer was washed with brine, dried over Na
column chromatography (CH Cl
2
SO
4
and concentrated in vacuo. Purification of the residue by
1
2
2
/MeOH, 100/1) gave 20 (49.0 g, 90%) as a colorless oil: H NMR (400
1
3
MHz, CDCl ) δ 2.49 (3H, s), 2.79 (2H, t, J = 5.8 Hz), 2.88-2.93 (2H, m), 3.58 (2H, s). C NMR (400
3
+
79
+
81
MHz, CDCl
3
) δ 26.7, 45.0, 52.0, 52.2, 130.1, 133.3, 149.1. MS (EI) m/z 232 (M , Br ), 234 (M , Br ).
+
81
HR-MS (EI; M , Br ) Calcd for C
7
9 2
H N BrS 233.9649, Found 233.9652.
Lithium 5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate (2)
To a stirred solution of 20 (48.9 g, 210 mmol) in dry Et O (500 mL) was added n-BuLi (1.53 M in
2
hexanes; 137 ml, 210 mmol) at -78 °C under an argon atmosphere. The reaction mixture was warmed
2
up to 0 °C, stirred for 20 min, and recooled to -78 °C. After the bubbling of CO gas for 5 min, the
reaction was warmed up to rt and concentrated in vacuo. Collection of the residue and washing with
1
hexane gave 2 (48.9 g, 99%) as a pale brown amorphous solid: H NMR (400 MHz, DMSO-d
6
) δ 2.37
+
(
3H, s), 2.64-2.77 (4H, m), 3.54 (2H, s). MS (FAB) m/z 199 (M + H) . Anal. Calcd for
C H N O LiS·1.6H O: C, 41.24; H, 5.28; N, 12.02. Found: C, 41.44; H, 4.89; N, 11.72.
8
9
2
2
2
Lithium 5-tert-Butoxycarbonyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate (3)