tert-Butyl 1-[3-({N-[(benzyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-fluorobenzyl]cyclopropanecarboxylate → (+/-)-tert-Butyl 1-{4-fluoro-3-[(4,4,4-trifluorovalyl)amino]benzyl}cyclopropanecarboxylate

HRID 626430Notes

Reaction equation

HRID 626430 reaction equation
C(OC([NH:11][C@H:12]([C:19]([NH:21][C:22]1[CH:23]=[C:24]([CH:36]=[CH:37][C:38]=1[F:39])[CH2:25][C:26]1([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:28][CH2:27]1)=[O:20])[CH:13]([C:15]([F:18])([F:17])[F:16])[CH3:14])=O)C1C=CC=CC=1>C(O)C.C1COCC1.[Pd]>[F:39][C:38]1[CH:37]=[CH:36][C:24]([CH2:25][C:26]2([C:29]([O:31][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:30])[CH2:28][CH2:27]2)=[CH:23][C:22]=1[NH:21][C:19](=[O:20])[C@H:12]([CH:13]([C:15]([F:18])([F:17])[F:16])[CH3:14])[NH2:11]

Participants

5

Reactant 1

HCID 118106680tert-Butyl 1-[3-({N-[(benzyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-fluorobenzyl]cyclopropanecarboxylate

Product 1

HCID 90015051(+/-)-tert-Butyl 1-{4-fluoro-3-[(4,4,4-trifluorovalyl)amino]benzyl}cyclopropanecarboxylate

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

5.31 g (9.61 mmol) of tert-butyl 1-[3-({N-[(benzyloxy)carbonyl]-4,4,4-trifluorovalyl}amino)-4-fluorobenzyl]cyclopropanecarboxylate (Example 32A, racemic diastereomer mixture) were dissolved in a mixture of 100 ml of ethanol and 20 ml of THF. The solution was inertized with argon, and 511 mg of palladium on carbon (10%) were added. The reaction mixture was stirred vigorously at standard pressure under an atmosphere of hydrogen overnight. After filtration through kieselguhr and washing with ethanol/THF, the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1→4:1) and the diastereomers were separated:

Workup

  1. additionwere added
  2. filtrationAfter filtration through kieselguhr
  3. washwashing with ethanol/THF
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1→4:1)
  6. customthe diastereomers were separated

Sources & evidence

ORD record
ord-4320e4ad3bb14dac9eaa3cee1da4efec
Source dataset
uspto-grants-2016_04
Patent number
US09309198B2

Reaction notes

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