Potassium Carbonate → (+)-1-(Cyclopropylmethyl)-3-(2,3-difluorophenyl)pyrrolidin-3-OL

HRID 1931837Notes

Reaction equation

HRID 1931837 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+].[CH:21]1([CH2:24]Br)[CH2:23][CH2:22]1>C(#N)C>[CH:21]1([CH2:24][N:11]2[CH2:12][CH2:13][C:9]([C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=3[F:1])([OH:14])[CH2:10]2)[CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 81503BromomethylcyclopropaneHCID 639883833-(2,3-Difluorophenyl)pyrrolidin-3-ol

Product 1

HCID 25143959(+)-1-(Cyclopropylmethyl)-3-(2,3-difluorophenyl)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 (0.58 g, 2.9 mmol), acetonitrile (20 mL), potassium carbonate (0.69 g, 5 mmol), cyclopropylmethyl bromide (0.308 mL, 3.18 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: 0.28 g. [α]D=−14.3° (methanol). The amine was converted to the oxalic acid salt and recrystallized from ethanol/diethyl ether: M.p. 172.8° C.; MS m/z (relative intensity, 70 eV) 253 (M+, 4) 55 (50), 141 (18), 127 (14), 96 (bp).

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: 0.28 g
  5. customrecrystallized from ethanol/diethyl ether

Sources & evidence

ORD record
ord-2eb1d32d63b94eb984886ba0ce221ed9
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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