Ethyl difluoroacetate → 5-(4,4-Difluoro-3-oxo-butyryl)-thiophene-2-carboxylic acid ethyl ester

HRID 572267Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([C:11](=[O:13])[CH3:12])=[CH:9][CH:10]=1)=[O:5])[CH3:2].[F:14][CH:15]([F:21])[C:16](OCC)=[O:17].C[O-].[Na+].[O-]CC.[Na+]>>[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([C:11](=[O:13])[CH2:12][C:16](=[O:17])[CH:15]([F:21])[F:14])=[CH:9][CH:10]=1)=[O:5])[CH3:2]

Participants

Reactant 4

HCID 9961Ethyl difluoroacetate

HCID 2723922Sodium ethoxide

HCID 10942334Sodium Methoxide

HCID 18737820Ethyl 5-acetylthiophene-2-carboxylate

Product 1

HCID 576061235-(4,4-Difluoro-3-oxo-butyryl)-thiophene-2-carboxylic acid ethyl esterYield 85%

Procedure

Prepared from 5-Acetyl-thiophene-2-carboxylic acid ethyl ester and ethyl difluoroacetate by the method described in Preparative Example 3. Sodium methoxide was substituted with sodium ethoxide. The product was obtained as a crude oil (5.4 g, 85%). An approx. 5:1 isomer mixture was observed in the NMR spectra of product. 1H NMR (CDCl3) 1.41 (t, J=7.0, 3H), 3.63 (q, J=7.0, 2H), 5.98 (t, minor isomer, J=53.2, 1H), 6.05 (t, major isomer, J=54.0, 1H), 6.45 (s, 1H), 7.74 (d, J=4.0, 1H), 7.80 (d, J=4.0, 1H). 19F NMR −127.8 (minor isomer, J=53.5), −127.1 (major isomer, J=55.5). LC/MS 5.18 min, [M+1]+ 277.

Sources & evidence

ORD record: ord-0555adbb725d459fbd1081c6875258f0
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029397B2

Reaction notes

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