Formic Acid → (S)-4-bromo-7-fluoro-2,3-dihydro-1H-inden-1-ol

HRID 625684Notes

Reaction equation

C(N(CC)CC)C.C(O)=O.[Br:11][C:12]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]2[C:13]=1[CH2:14][CH2:15][C:16]2=[O:22].O>ClCCl>[Br:11][C:12]1[CH:20]=[CH:19][C:18]([F:21])=[C:17]2[C:13]=1[CH2:14][CH2:15][C@@H:16]2[OH:22]

Participants

Conditions

Temperature: 0 °C

Procedure

Triethylamine (26.2 mL, 187 mmol) is dissolved in dichloromethane (100 mL) and cooled to 0° C. then formic acid (7.96 mL, 211 mmol) is added dropwise with cooling. 4-Bromo-7-fluoro-indan-1-one (European patent EP2042480, 13.8 g, 60 mmol) is added and the mixture degassed with a flow of argon. Chloro([1S,2S)-(+2-amino-1,2-diphenylethyl](4-toluenesulfonyl)amido)(mesitylene)ruthenium(II) complex (375 mg, 0.6 mmol) is added and the mixture is stirred overnight at room temperature. Water is added, the mixture shaken and the phases separated. The organic phase is dried and concentrated under vacuum. The residue is purified by flash chromatography (0-20% ethyl acetate in cyclohexane) to give the title compound (Yield 13.1 g). GC (METHOD 1): tR=9.35 min; Mass spectrum (EI+): m/z=229, 231 [M]+, e.e. 100% by chiral HPLC (Column: Daicel Chiralcel OJ-H, 4.6×250 mm, 5 μm Mobile phase: hexane:ethanol 95:5, 1 mL/min, 25° C.) tR=9.87 min.

Workup

temperaturewith cooling
customthe mixture degassed with a flow of argon
additionChloro([1S,2S)-(+2-amino-1,2-diphenylethyl](4-toluenesulfonyl)amido)(mesitylene)ruthenium(II) complex (375 mg, 0.6 mmol) is added
stirringthe mixture shaken
customthe phases separated
customThe organic phase is dried
concentrationconcentrated under vacuum
customThe residue is purified by flash chromatography (0-20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record: ord-0b54285fd7ef489b9659e676b1e6375c
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09308194B2

Reaction notes

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