Water → Ethyl (2S)-3-[3-({(3R)-N-[(benzyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-chlorophenyl]-2-methylpropanoate

HRID 626428Notes

Reaction equation

HRID 626428 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:19]([OH:21])=O)[C@H:13]([C:15]([F:18])([F:17])[F:16])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:22][C:23]1[CH:24]=[C:25]([CH2:30][C@H:31]([CH3:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:26]=[CH:27][C:28]=1[Cl:29].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O>CN(C=O)C.N1C=CC=CC=1>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:19]([NH:22][C:23]1[CH:24]=[C:25]([CH2:30][C@H:31]([CH3:37])[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:26]=[CH:27][C:28]=1[Cl:29])=[O:21])[C@H:13]([C:15]([F:16])([F:17])[F:18])[CH3:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58288362(+)-ethyl (2S)-3-(3-amino-4-chlorophenyl)-2-methylpropanoateHCID 118106631(3R)-N-[(Benzyloxy)carbonyl]-4,4,4-trifluorovaline

Product 1

HCID 131735218Ethyl (2S)-3-[3-({(3R)-N-[(benzyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-chlorophenyl]-2-methylpropanoate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

1.26 g (purity 76%, about 3.14 mmol) of (3R)—N-[(benzyloxy)carbonyl]-4,4,4-trifluorovaline (diastereomer mixture) and 0.91 g (3.76 mmol) of (+)-ethyl (2S)-3-(3-amino-4-chlorophenyl)-2-methylpropanoate were dissolved in a mixture of 10 ml of DMF and 4 ml of pyridine, and 1.55 g (4.08 mmol) of HATU were added at RT. The reaction mixture was stirred at RT overnight and then added to water. The mixture was extracted three times with ethyl acetate, and the combined organic phases were then washed successively with sat. sodium bicarbonate solution, 1 N hydrochloric acid and sat. sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The resulting solid was stirred in a mixture of cyclohexane and diethyl ether (about 3:1), filtered off with suction and dried under high vacuum. This gave 0.99 g of the target product (59.9% of theory, diastereomer ratio about 7:1).

Workup

  1. additionwere added at RT
  2. extractionThe mixture was extracted three times with ethyl acetate
  3. washthe combined organic phases were then washed successively with sat. sodium bicarbonate solution, 1 N hydrochloric acid and sat. sodium chloride solution
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated under reduced pressure
  6. stirringThe resulting solid was stirred in a mixture of cyclohexane and diethyl ether (about 3:1)
  7. filtrationfiltered off with suction
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-ad127d12e3c74432adc3e5a2a4813ff1
Source dataset
uspto-grants-2016_04
Patent number
US09309198B2

Reaction notes

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