Methanol → (3S,9aS)-tert-butyl 3-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)hexahydropyrazino[2,1-c][1,4]thiazine-8(1H)-carboxylate
Reaction equation
C([S:4][CH2:5][C@H:6]1[N:11]([CH2:12][CH:13](Cl)[C:14]2[C:15]([CH3:24])=[C:16]3[C:20](=[CH:21][CH:22]=2)[C:19](=[O:23])[O:18][CH2:17]3)[CH2:10][CH2:9][N:8]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:7]1)(=O)C.C[O-].[Na+].CO>C1COCC1>[CH3:24][C:15]1[C:14]([C@@H:13]2[S:4][CH2:5][C@@H:6]3[CH2:7][N:8]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:9][CH2:10][N:11]3[CH2:12]2)=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][O:18][C:19]2=[O:23]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of (3S)-tert-butyl 3-(acetylthiomethyl)-4-(2-chloro-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)piperazine-1-carboxylate (596 mg, 1.234 mmol) in anhydrous THF (20 mL) was treated dropwise with sodium methoxide, 25% solution in methanol (0.846 mL, 3.70 mmol). The reaction mixture was stirred for 2 hours under nitrogen at room temperature. LCMS showed formation of the desired product. Solvent was removed under reduced pressure. Residue was redissolved in dichloromethane and washed with brine. Organic layer was dried over MgSO4, filtered and concentrated. Residue was purified on Biotage SP1, eluting with 20-80% ethyl acetate/hexanes, 16 CV: 1H NMR (500 MHz, CDCl3) δ 8.64 (d, J=8.0 Hz, 1H), 7.77 (d, J=8.0 Hz, 1H), 5.29 (s, 2H), 3.81-4.20 (m, 3H), 3.38 (dd, J=2.3, 12.6 Hz), 3.00-3.22 (m, 2H), 2.57-2.82 (m, 2H), 2.24-2.56 (m, 7H), 1.51 (s, 9H).
Sources & evidence
- ORD record
- ord-d3934540dd7f4841bdaabf66125aff56
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09062070B2
Reaction notes
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