Methyl 2-{[(benzyloxy)carbonyl]amino}-2-(dimethyl phosphono)acetate → Methyl(2Z)-2-{[(benzyloxy)carbonyl]amino}-3-(6-trifluoromethylpyridin-3-yl)acrylate

HRID 2237375Notes

Reaction equation

[F:1][C:2]([F:12])([F:11])[C:3]1[N:8]=[CH:7][C:6]([CH:9]=O)=[CH:5][CH:4]=1.[CH2:13]([O:20][C:21]([NH:23][CH:24](P(OC)(OC)=O)[C:25]([O:27][CH3:28])=[O:26])=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1>[CH2:13]([O:20][C:21]([NH:23]/[C:24](=[CH:9]\[C:6]1[CH:7]=[N:8][C:3]([C:2]([F:12])([F:11])[F:1])=[CH:4][CH:5]=1)/[C:25]([O:27][CH3:28])=[O:26])=[O:22])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

Conditions

Temperature: -70 °C

Procedure

6-Trifluoromethylpyridine-3-carbaldehyde (4.85 g, 27.70 mmol) and methyl {[benzyloxycarbonyl]amino}(dimethoxyphosphoryl)acetate (9.17 g, 27.70 mmol, 1.0 equivalent) are dissolved in THF (70 ml) and cooled to −70° C. At −70° C., N,N,N,N-tetramethylguanidine (6.38 g, 55.39 mmol, 6.95 ml, 2.0 equivalents) is slowly added dropwise and then the mixture is stirred at −70° C. for 4 h, subsequently at RT for 12 h. The reaction mixture is concentrated, and extracted with ethyl acetate (2×100 ml) against water. The combined organic phases are washed with a saturated sodium chloride solution, dried over sodium sulfate and filtered. After concentration, the crude product is chromatographed (silica gel, eluent: toluene, then toluene: ethyl acetate 10:1). 6.93 g (66% of theory) of the title compound are obtained.

Workup

concentrationThe reaction mixture is concentrated
extractionextracted with ethyl acetate (2×100 ml) against water
washThe combined organic phases are washed with a saturated sodium chloride solution
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationAfter concentration
customthe crude product is chromatographed (silica gel, eluent

Sources & evidence

ORD record: ord-ebfb01817613454ea32ffd6c2b7f040c
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07718611B2

Reaction notes

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