Hydrogen Bromide → Methyl (S)-2-amino-4,4-difluoro-5-phenylpentanoate

HRID 1913340Notes

Reaction equation

HRID 1913340 reaction equation
C(OC([NH:11][C@@H:12]([CH2:17][C:18]([F:27])([F:26])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:13]([O:15][CH3:16])=[O:14])=O)C1C=CC=CC=1.Br.C(OCC)C>C(O)(=O)C>[NH2:11][C@@H:12]([CH2:17][C:18]([F:26])([F:27])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:13]([O:15][CH3:16])=[O:14]

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 3283Diethyl EtherHCID 57535357Methyl (S)-2-benzyloxycarbonylamino-4,4-difluoro-5-phenylpentanoate

Product 1

HCID 59430997Methyl (S)-2-amino-4,4-difluoro-5-phenylpentanoate

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

3.0 g of methyl (S)-2-benzyloxycarbonylamino-4,4-difluoro-5-phenylpentanoate (8.0 mmol) were admixed with 8.0 ml (5 eq.) of a 30% HBr solution in glacial acetic acid with ice bath cooling and stirred for 3 h. 100 ml of diethyl ether were added and the resulting precipitate was filtered off with suction. The crude product thus obtained was purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA). The amorphous solid obtained after freeze-drying was taken up in dichloromethane and washed with sat. NaHCO3 solution. The organic phase was dried over MgSO4 and concentrated under reduced pressure. Thus, methyl (S)-2-amino-4,4-difluoro-5-phenyl-pentanoate was obtained as a yellow oil.

Workup

  1. temperaturecooling
  2. filtrationthe resulting precipitate was filtered off with suction
  3. customThe crude product thus obtained
  4. customwas purified by preparative HPLC (gradient: acetonitrile/water and addition of 0.05% TFA)
  5. customThe amorphous solid obtained
  6. customafter freeze-drying
  7. washwashed with sat. NaHCO3 solution
  8. dry with materialThe organic phase was dried over MgSO4
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-15cee02eb50b4064905657c08fc176b6
Source dataset
uspto-grants-2013_12
Patent number
US08609681B2

Reaction notes

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