Benzeneacetonitrile, 3-fluoro- → Methyl 4-cyano-3-(p-fluorophenyl)-4-(m-fluorophenyl)butyrate

HRID 1525573Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]#[N:10])[CH:5]=[CH:6][CH:7]=1.C[O-].[Na+].[F:14][C:15]1[CH:20]=[CH:19][C:18]([CH:21]=[CH:22][C:23]([O:25][CH3:26])=[O:24])=[CH:17][CH:16]=1.C(CC(C1C=CC(F)=CC=1)C(C1C=CC=C(F)C=1)C(OC)=O)#N>C1(C)C=CC=CC=1>[C:9]([CH:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1)[CH:21]([C:18]1[CH:17]=[CH:16][C:15]([F:14])=[CH:20][CH:19]=1)[CH2:22][C:23]([O:25][CH3:26])=[O:24])#[N:10]

Participants

Conditions

Temperature: 65 °C

Procedure

Under protective gas (Ar), 0.767 g (5.0 mmol) of (3-fluorophenyl)acetonitrile and 0.1 ml of sodium methoxide solution (30% in methanol) were added to 0.820 g (4.55 mmol) of methyl 3-(4-fluorophenyl)acrylate in 15.0 ml of toluene, and the mixture was stirred in a closed vessel at 65° C. for 15 h. The solvent was removed under reduced pressure, the residue was taken up in ethyl acetate and the mixture was washed twice with in each case 25 ml of water. The combined organic phases were dried over sodium sulphate and the solvent was removed under reduced pressure. Chromatography of the residue on silica gel (ethyl acetate/heptane=20:80) gave 0.950 g (57% of theory) of an erythro/threo diastereomer mixture of methyl 4-cyano-(3-fluorophenyl)-3-(4-fluorophenyl)butanoate (erythro:threo=54:46 according to integration of the methyl singlets in the 1H-NMR in CDCl3 at 3.66 and 3.56 ppm).

Workup

customThe solvent was removed under reduced pressure
washthe mixture was washed twice with in each case 25 ml of water
dry with materialThe combined organic phases were dried over sodium sulphate
customthe solvent was removed under reduced pressure
customChromatography of the residue on silica gel (ethyl acetate/heptane=20:80) gave

Sources & evidence

ORD record: ord-20dbac19d8fd4496be9f4241ce4647b6
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09084425B2

Reaction notes

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