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

HRID 626422Notes

Reaction equation

HRID 626422 reaction equation
[F:1][C:2]([F:13])([F:12])[C@H:3]([CH3:11])[C@@H:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[NH2:5].C(N(CC)CC)C.[CH2:21]([O:28][C:29](ON1C(=O)CCC1=O)=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1COCC1.C(OCC)(=O)C>[CH2:21]([O:28][C:29]([NH:5][C@H:4]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[C@H:3]([C:2]([F:12])([F:13])[F:1])[CH3:11])=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 83172Benzyl succinimido carbonateHCID 124507558Ethyl (3R)-4,4,4-trifluorovalinate

Product 1

HCID 131735215Ethyl (3R)-N-[(benzyloxy)carbonyl]-4,4,4-trifluorovalinate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

23.5 g of ethyl (3R)-4,4,4-trifluorovalinate (diastereomer mixture, crude product about 70%) and 18.1 ml (130 mmol) of triethylamine were dissolved in 235 ml of THF, and 32.3 g (130 mmol) of N-(benzyloxycarbonyloxy)succinimide were added. The reaction mixture was stirred at RT overnight and then diluted with ethyl acetate. The mixture was washed successively with sat. sodium bicarbonate solution, 1 N hydrochloric acid and sat. sodium chloride solution. The organic phase was dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1). This gave 22.1 g of the target product (about 80% of theory, diastereomer ratio about 2:1).

Workup

  1. washThe mixture was washed successively with sat. sodium bicarbonate solution, 1 N hydrochloric acid and sat. sodium chloride solution
  2. dry with materialThe organic phase was dried over magnesium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1)

Sources & evidence

ORD record
ord-644dfd2ddfac4395b34d51c7104b1398
Source dataset
uspto-grants-2016_04
Patent number
US09309198B2

Reaction notes

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