Acetonitrile → HCID 25143814, compound

HRID 1931826Notes

Reaction equation

HRID 1931826 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(#N)C.C(=O)([O-])[O-].[K+].[K+].[CH2:24](Br)[CH2:25][CH2:26][CH3:27]>O>[CH2:24]([N:11]1[CH2:12][CH2:13][C:9]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=2[F:1])([OH:14])[CH2:10]1)[CH2:25][CH2:26][CH3:27]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 8002Butyl bromide2×HCID 11430Potassium CarbonateHCID 639883833-(2,3-Difluorophenyl)pyrrolidin-3-ol

Product 1

HCID 25143814HCID 25143814, compoundYield 54.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In a sealed tube a mixture of 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) and n-butylbromide (0.25 mL, 2.6 mmol) was stirred at ambient temperature for 30 min after which an additional amount of n-butylbromide (0.12 mL, 1.25 mmol) was added and the mixture was stirred for 1 h. Water was added and the aqueous phase was extracted with ethyl acetate. The combined organic phase was dried (Na2SO4) and evaporated. Purification by flash chromatography on silica gel (ethyl acetate/methanol, 1:1) gave the title compound (0.35 g). [α]D=−26° (methanol). The amine was converted to the oxalic acid salt and recrystallized from ethanol/diethyl ether: M.p. 155.3° C.; MS m/z (relative intensity, 70 eV) 255 (M+, 8), 182 (30), 98 (25), 57 (16), 212 (bp).

Workup

  1. additionwas added
  2. extractionthe aqueous phase was extracted with ethyl acetate
  3. dry with materialThe combined organic phase was dried (Na2SO4)
  4. customevaporated
  5. customPurification by flash chromatography on silica gel (ethyl acetate/methanol, 1:1)

Sources & evidence

ORD record
ord-f816a207ed2f4486996b46db05eecd82
Source dataset
uspto-grants-2012_05
Patent number
US08188301B2

Reaction notes

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