Methanol → (R)-2-Methyl-N-((R)-6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl)propane-2-sulfinamide
Reaction equation
[BH4-].[Na+].[CH3:3][C:4]([S@:7]([N:9]=[C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]([F:22])([F:21])[F:20])[CH:17]=2)[CH2:12][CH2:11]1)=[O:8])([CH3:6])[CH3:5].C1COCC1.CO>C(=O)=O>[CH3:6][C:4]([S@:7]([NH:9][C@H:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]([F:20])([F:21])[F:22])[CH:17]=2)[CH2:12][CH2:11]1)=[O:8])([CH3:3])[CH3:5]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
Sodium borohydride (756 mg, 20.0 mmol) was stirred in a round-bottomed flask under argon at −40 to −50° C. The reaction mixture of Intermediate 15A was added dropwise to the flask, and THF was added to the reaction mixture (ca. 0.6 M). The resulting mixture was allowed to warm up to 0° C. during 1.5 h period. The reaction mixture was cooled in dry ice and MeOH was added dropwise until gas evolution stopped. The mixture was stirred at rt for 20 min, filtered through Celite® and rinsed with EtOAc then CH2Cl2. The filtrate was washed with brine (2×) and dried over MgSO4, filtered and concentrated. The residue was purified on ISCO (hexanes/EtOAc) to give Intermediate 15B (370 mg, 1.21 mmol, 26.7% yield) as colorless crystals. LC-MS (ESI) 306.0 (M+H), RT=2.10 min (Method B).
Workup
- filtrationfiltered through Celite®
- washrinsed with EtOAc
- washThe filtrate was washed with brine (2×)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified on ISCO (hexanes/EtOAc)
Sources & evidence
- ORD record
- ord-a50be4ff2ca64f23af290c20a39cf7d8
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08946430B2
Reaction notes
Loading…