Water → 7-chloro-2-[(S)-2-(methoxymethyl)pyrrolidine-1-carbonyl]thieno[3,2-b]pyridine
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([O-:13])=O)[S:10][C:3]=12.[Li+].[CH:15]([N:18]([CH:21]([CH3:23])[CH3:22])CC)([CH3:17])C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.O.CN([CH:61]=[O:62])C>>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([N:18]3[CH2:15][CH2:17][CH2:23][C@H:21]3[CH2:22][O:62][CH3:61])=[O:13])[S:10][C:3]=12Participants
Procedure
To a mixture of lithium 7-chlorothieno[3,2-b]pyridine-2-carboxylate (6.59 g, 30 mmole) in DMF (100 ml) were added diisopropylethylamine, (6 ml, 4.45 g, 34.4 mmole), benzotriazol-1-yloxytris(pyrrolidino)phosphonium hexafluorophosphate (16.16 g, 31 mmole) and S-(+)-2-(methoxymethyl)pyrrolidine (3.73 g, 32.4 mmole). The resultant reaction mixture was stirred at ambient temperature for 16 hours. The crude reaction mixture was poured into water (600 ml) and extracted with EtOAc (3×200 ml). The combined organic extracts were washed with water (4×200 ml), dried over Na2SO4 and concentrated, in vacuo, to give 8.8 g of an amber oil, which was purified by silica gel chromatography. Elution with Et2O:EtOAc (67:33) and evaporation of the appropriate fractions gave 6.89 g (74%) of an orange syrup. 1H NMR (DMSO-d6): δ8.62 (1H, d, J=5.0 Hz), 7.88 (1H, s), 7.35 (1H, d, J=5.0 Hz), 4.54-4.47 (1H, m), 3.93-3.75 (2H, m), 3.71-3.55 (2H, m), 3.37 (3H, s), 2.15-1.92 (4H, m). Anal. Calcd. for C14H15N2O2SCl: C, 54.10; H, 4.87; N, 9.01; S, 10.32; Cl, 11.41. Found: C, 53.96;
Workup
- customThe resultant reaction mixture
- customThe crude reaction mixture
- extractionextracted with EtOAc (3×200 ml)
- washThe combined organic extracts were washed with water (4×200 ml)
- dry with materialdried over Na2SO4
- concentrationconcentrated, in vacuo
Sources & evidence
- ORD record
- ord-d775a1d738f14c91a116a679ab77e44d
- Source dataset
- uspto-grants-2005_03
- Patent number
- US06869962B2
Reaction notes
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