Citric Acid → HCID 50916498, compound

HRID 389406Notes

Reaction equation

C([Mg]Br)C.CCOCC.[CH:10]1([C:13]#[CH:14])[CH2:12][CH2:11]1.[C:15]([O:21][C@H:22]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:23]([NH:25][C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=1[C:33](=[O:38])[C:34]([F:37])([F:36])[F:35])=[O:24])(=[O:20])[C:16]([CH3:19])([CH3:18])[CH3:17].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[C:15]([O:21][C@H:22]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:23]([NH:25][C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=1[C@@:33]([OH:38])([C:14]#[C:13][CH:10]1[CH2:12][CH2:11]1)[C:34]([F:36])([F:37])[F:35])=[O:24])(=[O:20])[C:16]([CH3:19])([CH3:18])[CH3:17]

Participants

Conditions

Temperature: 0 °C

Procedure

Ethylmagnesium bromide 3 M in ether (2 mL, 6.2 mmol) was added slowly to a solution of cyclopropyl acetylene (0.41 g, 6.2 mmol) in THF (5 mL) in an ice-bath under argon. The mixture was stirred at 0° C. for 1 hour and then 40° C. for 2 hours. Then (R)-2-(4-chloro-2-(2,2,2-trifluoroacetyl)phenylamino)-2-oxo-1-phenylethyl pivalate (12, 0.55 g, 1.24 mmol) in THF (2 mL) was added slowly in an ice-bath. The mixture was stirred at 0° C. for 1.5 hours. 10% Citric acid was added to quench the reaction. The organic layer was washed with water and then evaporated to dryness to give (R)-2-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenylamino)-2-oxo-1-phenylethyl pivalate (13). This solid was shown to be 35.9% de by chiral HPLC. The pure product was isolated by chromatography.

Workup

wait40° C. for 2 hours
stirringThe mixture was stirred at 0° C. for 1.5 hours
customto quench
customthe reaction
washThe organic layer was washed with water
customevaporated to dryness

Sources & evidence

ORD record: ord-6ea2755afaae47368506aa4e765c8af2
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08378143B2

Reaction notes

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