Methanol → (R)-2-Methyl-N-((R)-6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl)propane-2-sulfinamide

HRID 1497022Notes

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

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 4A 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 by flash chromatography (hexanes/EtOAc) to give Intermediate 4B (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 by flash chromatography (hexanes/EtOAc)

Sources & evidence

ORD record: ord-70d01dfca7fc423db944775667c1d12b
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199946B2

Reaction notes

Loading…