Potassium Carbonate → (-)-3-(2,3-Difluorophenyl)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-OL

HRID 1931836Notes

Reaction equation

HRID 1931836 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1([OH:14])[CH2:13][CH2:12][NH:11][CH2:10]1.C(=O)([O-])[O-].[K+].[K+].[F:21][C:22]([F:27])([F:26])[CH2:23][CH2:24]I>C(#N)C>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1([OH:14])[CH2:13][CH2:12][N:11]([CH2:24][CH2:23][C:22]([F:27])([F:26])[F:21])[CH2:10]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1561651,1,1-Trifluoro-3-iodopropaneHCID 639883833-(2,3-Difluorophenyl)pyrrolidin-3-ol

Product 1

HCID 25143958(-)-3-(2,3-Difluorophenyl)-1-(3,3,3-trifluoropropyl)pyrrolidin-3-OL

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Preparation according to Example 43: Enantiomer E2 of 3-(2,3-difluorophenyl)-pyrrolidin-3-ol (0.5 g, 2.5 mmol), acetonitrile (20 mL), potassium carbonate (0.69 g, 5 mmol), 1,1,1-trifluoro-3-iodopropane (0.32 mL, 3.1 mmol). Stirred 2 h at ambient temperature and 2×5 min at 40° C.; Purification by flash chromatography on silica gel (ethyl acetate/methanol, 4:1) Yield: 0.2 g. [α]D=−14.6° (methanol). The amine was converted to the oxalic acid salt and recrystallized from ethanol/diethyl ether: M.p. 144° C.; MS m/z (relative intensity, 70 eV) 295 (M+, 24), 212 (31), 182 (12), 139 (bp), 127 (20).

Workup

  1. customPreparation
  2. custom2×5 min
  3. customat 40° C.
  4. customPurification by flash chromatography on silica gel (ethyl acetate/methanol, 4:1) Yield: 0.2 g
  5. customrecrystallized from ethanol/diethyl ether

Sources & evidence

ORD record
ord-d2e02ae285494351a80545a09a9192f7
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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