Water → (+/-)-tert-Butyl 1-[3-({cyclopentyl[4-(2,2-difluorovinyl)phenyl]acetyl}amino)benzyl]cyclopropanecarboxylate

HRID 1475657Notes

Reaction equation

HRID 1475657 reaction equation
Cl[C:2]([F:7])([F:6])[C:3]([O-])=O.[Na+].[CH:9]1([CH:14]([C:35]2[CH:40]=[CH:39][C:38](C=O)=[CH:37][CH:36]=2)[C:15]([NH:17][C:18]2[CH:19]=[C:20]([CH:32]=[CH:33][CH:34]=2)[CH2:21][C:22]2([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:24][CH2:23]2)=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>C(OCC)(=O)C>[CH:9]1([CH:14]([C:35]2[CH:40]=[CH:39][C:38]([CH:3]=[C:2]([F:7])[F:6])=[CH:37][CH:36]=2)[C:15]([NH:17][C:18]2[CH:19]=[C:20]([CH:32]=[CH:33][CH:34]=2)[CH2:21][C:22]2([C:25]([O:27][C:28]([CH3:30])([CH3:31])[CH3:29])=[O:26])[CH2:23][CH2:24]2)=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10]1

Participants

6

Reactant 4

HCID 962WaterHCID 11776TriphenylphosphineHCID 2734985Sodium chlorodifluoroacetateHCID 86667523(+/-)-Tert-butyl 1-(3-{[cyclopentyl(4-formylphenyl)acetyl]-amino}benzyl)cyclopropanecarboxylate

Product 1

HCID 66563353(+/-)-tert-Butyl 1-[3-({cyclopentyl[4-(2,2-difluorovinyl)phenyl]acetyl}amino)benzyl]cyclopropanecarboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

At 60° C., 475.6 mg (3.12 mmol) of sodium chloro(difluoro)acetate were added to a mixture of 800.0 mg (1.73 mmol) of (+/−)-tert-butyl 1-(3-{[cyclopentyl(4-formylphenyl)acetyl]-amino}benzyl)cyclopropanecarboxylate and 681.9 mg (2.60 mmol) of triphenylphosphine. The mixture was heated to 110° C. and stirred at this temperature for 30 min. After cooling, the mixture was poured into water. Ethyl acetate was added, and the organic phase was separated off, washed with saturated sodium chloride solution, dried with magnesium sulphate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (mobile phase acetonitrile/water). This gave 319.2 mg (37.2% of theory) of the target compound.

Workup

  1. temperatureAfter cooling
  2. customthe organic phase was separated off
  3. washwashed with saturated sodium chloride solution
  4. dry with materialdried with magnesium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by preparative RP-HPLC (mobile phase acetonitrile/water)

Sources & evidence

ORD record
ord-34afe3328bf447babdfd93a21b882cbc
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

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