Ammonium Chloride → Ethyl 4-benzyloxycarbonylamino-2,2-difluoro-3-hydroxy-5-phenylpentanoate

HRID 1859642Notes

Reaction equation

HRID 1859642 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH:12]([CH:20]=[O:21])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:23]([F:30])([F:29])[C:24]([O:26][CH2:27][CH3:28])=[O:25].[Cl-].[NH4+]>[Zn].C1COCC1>[CH2:1]([O:8][C:9]([NH:11][CH:12]([CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[CH:20]([OH:21])[C:23]([F:30])([F:29])[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 25517Ammonium Chloride2×HCID 69585Ethyl bromodifluoroacetateHCID 11323549Benzyl (1-oxo-3-phenylpropan-2-yl)carbamate

Product 1

HCID 10549370Ethyl 4-benzyloxycarbonylamino-2,2-difluoro-3-hydroxy-5-phenylpentanoateYield 91.3%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of the objective compound of step (10) (42.8 g, 0.151 mol), zinc dust (15.9 g, 0.243 mol) and THF (105 ml) was added ethyl bromodifluoroacetate (31.6 mL, 0.246 mol) with dropwise over 2 hours at 26˜49° C. The resulting mixture was stirred at room temperature for 2 hours. To this reaction mixture was added saturated ammonium chloride aqueous solution (110 mL), and the mixture was stirred for a few minutes. The obtained mixture was added to saturated ammonium chloride aqueous solution (650 mL) and extracted with ethyl acetate (500 mL, 2×300 mL). The extract was washed with saturated brine (400 mL), dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (2:1 hexane-ethyl acetate) to give 56.15 g of ethyl 4-benzyloxycarbonylamino-2,2-difluoro-3-hydroxy-5-phenylpentanoate as a light-yellow oil (a mixture of diastereomers, 75%).

Workup

  1. stirringthe mixture was stirred for a few minutes
  2. extractionextracted with ethyl acetate (500 mL, 2×300 mL)
  3. washThe extract was washed with saturated brine (400 mL)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (2:1 hexane-ethyl acetate)

Sources & evidence

ORD record
ord-0bd87b20f67f4ce6a452470c93db8873
Source dataset
uspto-grants-2003_03
Patent number
US06528514B1

Reaction notes

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