Triethylamine → Ethyl (3R)-N-[(allyloxy)carbonyl]-4,4,4-trifluorovalinate

HRID 626424Notes

Reaction equation

C(N(CC)CC)C.C1(=O)NC(=O)CC1.Cl[C:16]([O:18][CH2:19][CH:20]=[CH2:21])=[O:17].[F:22][C:23]([F:34])([F:33])[C@H:24]([CH3:32])[C@@H:25]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[NH2:26]>C(OCC)(=O)C.C1COCC1>[CH2:19]([O:18][C:16]([NH:26][C@H:25]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[C@H:24]([C:23]([F:34])([F:33])[F:22])[CH3:32])=[O:17])[CH:20]=[CH2:21]

Participants

Conditions

Temperature: 0 °C

Procedure

9.7 ml (69.3 mmol) of triethylamine were added dropwise to a solution of 6.38 g (55.4 mmol) of succinimide in 90 ml of abs. THF. The resulting suspension was cooled to 0° C., and a solution of 6.68 g (55.4 mmol) of allyl chloroformate in 10 ml of abs. THF was added dropwise. The mixture was stirred at 0° C. for 1 h, and three portions of in total 9.2 g (about 46 mmol) of ethyl (3R)-4,4,4-trifluorovalinate (diastereomer mixture, crude product) were added. The reaction mixture was warmed to RT overnight, then diluted with ethyl acetate, washed with sat. sodium bicarbonate solution and sat. sodium chloride solution, dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 10:1→4:1). This gave 6.50 g of the target product (about 50% of theory, diastereomer ratio about 2:1).

Workup

temperatureThe reaction mixture was warmed to RT overnight
washwashed with sat. sodium bicarbonate solution and sat. sodium chloride solution
dry with materialdried over sodium sulphate
concentrationconcentrated under reduced pressure
customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 10:1→4:1)

Sources & evidence

ORD record: ord-3fe86a5cfd3b4932aa9e84601ab655f1
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09309198B2

Reaction notes

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