Formaldehyde → (+)-3-(2,3-Difluorophenyl)-1-methylpyrrolidin-3-OL

HRID 1931847Notes

Reaction equation

HRID 1931847 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.[CH2:15]=O>C(O)=O>[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]([CH3:15])[CH2:10]1

Participants

4

Reactant 2

HCID 712Formaldehyde2×HCID 639883833-(2,3-Difluorophenyl)pyrrolidin-3-ol

Product 1

HCID 25143816(+)-3-(2,3-Difluorophenyl)-1-methylpyrrolidin-3-OL

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

Preparation according to Example 11: Enantiomer E1 of 3-(2,3-difluorophenyl)-pyrrolidin-3-ol (0.15 g, 0.72 mmol), formic acid (1.95 mL), aqueous formaldehyde (40%, 2.17 mL). The mixture was stirred for 5 h after which additional aqueous formaldehyde (1.5 mL) was added and the mixture was refluxed overnight. Purification by flash chromatography on silica gel (ethyl acetate/methanol, 10:1). Yield: 0.09 g. [α]D=+19.1°; The amine was converted to the oxalic acid salt and recrystallized from ethanol/diethyl ether/diisopropyl ether; M.p. 131-132° C.; MS m/z (relative intensity, 70 eV) 213 (M+, 15), 57 (bp), 58 (28), 141 (15), 127 (10), 113 (10).

Workup

  1. customPreparation
  2. additionwas added
  3. temperaturethe mixture was refluxed overnight
  4. customPurification by flash chromatography on silica gel (ethyl acetate/methanol, 10:1)
  5. customrecrystallized from ethanol/diethyl ether/diisopropyl ether

Sources & evidence

ORD record
ord-d5604233f2d14edabafe17704d277391
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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