Formaldehyde → N-[4-(2-butylacryloyl)-2-fluorophenyl]-2,2-dimethylpropanamide

HRID 1372501Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([C:8](=[O:14])[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[CH:5]=[CH:4][C:3]=1[NH:15][C:16](=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18].[C:22]([O-])([O-])=O.[K+].[K+].C=O>CO.C(Cl)Cl>[CH2:10]([C:9](=[CH2:22])[C:8]([C:6]1[CH:5]=[CH:4][C:3]([NH:15][C:16](=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18])=[C:2]([F:1])[CH:7]=1)=[O:14])[CH2:11][CH2:12][CH3:13]

Participants

Conditions

Temperature: 55 °C

Procedure

A solution of N-(2-fluoro-4-hexanoylphenyl)-2,2-dimethylpropanamide (17.8 g, 60.7 mmol) in methanol (75 mL) was treated successively with K2CO3 (8.4 g, 60.7 mmol) and formaldehyde (37 wt. % solution in water, 5.0 mL, 67 mmol). The mixture was placed under a nitrogen atmosphere, stirred, and heated in an oil bath at 55° C. for 4 hours. After cooling to room temperature, the mixture was diluted with CH2Cl2 (300 mL), dried over MgSO4, and filtered through a pad of silica gel, using more CH2Cl2 (200 mL) to wash the pad. The filtrate and washings were concentrated under vacuum to provide a mixture (19.5 g) of N-[4-(2-butylacryloyl)-2-fluorophenyl]-2,2-dimethylpropanamide, N-{2-fluoro-4-[2-(hydroxymethyl)hexanoyl]phenyl]-2,2-dimethylpropanamide, and N-{2-fluoro-4-[2-(methoxymethyl)hexanoyl]phenyl]-2,2-dimethylpropanamide.

Workup

temperatureAfter cooling to room temperature
dry with materialdried over MgSO4
filtrationfiltered through a pad of silica gel
washto wash the pad
concentrationThe filtrate and washings were concentrated under vacuum

Sources & evidence

ORD record: ord-35edc2300df541d58e213ac38bb33353
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07157604B2

Reaction notes

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