Benzyl chloroformate → HCID 53668353, compound

HRID 617751Notes

Reaction equation

HRID 617751 reaction equation
[C@H:1]12[CH2:17][C@H:4]([N:5]([C:7]3[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][C:8]=3[F:16])[CH2:6]1)[CH2:3][O:2]2.C1COCC1.O.C([O-])([O-])=O.[K+].[K+].Cl[C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32]>[Pd].CC#N.C(Cl)(Cl)Cl.C(O)(=O)C>[C:31]([NH:13][C:10]1[CH:11]=[CH:12][C:7]([N:5]2[CH2:6][C@@H:1]3[CH2:17][C@H:4]2[CH2:3][O:2]3)=[C:8]([F:16])[CH:9]=1)([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32]

Participants

8

Reactant 4

HCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 21881883Oxolane--water (1/1)HCID 53799421HCID 53799421, compound

Product 1

HCID 53668353HCID 53668353, compoundYield 98.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 22555007Acetonitrile chloroformSolvent2×

Procedure

A solution of 4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-3-fluoronitrobenzene (0.160 g, 0.672 mmol) in 3:1 THF/H2O (4 mL) was treated with acetic acid (0.115 mL) and then 10% palladium/carbon (0.020 g) under a N2 stream. The atmosphere was replaced with H2 (balloon) by repeated evacuation and filling and the mixture stirred at ambient temperature. After 2 h, TLC analysis (6% CH3CN/CHCl3) revealed the reduction to be complete. The reaction mixture was filtered through Celite® and the filtrate immediately placed under an atmosphere of N2 and treated with K2CO3 (0.464 g, 3.36 mmol) followed by benzyl chloroformate (0.117 mL, 0.864 mmol). TLC analysis (6% CH3CN/CHCl3) after 0.5 h revealed the reaction to be complete. The reaction mixture was concentrated under reduced pressure and chromatographed over silica gel (20 g), eluting with a gradient of 1-5% CH3CN/CHCl3. Concentration of appropriate fractions afforded 0.226 g (98%) of the title compound as a white solid with mp 120-121° C. and MS(EI) 342 (M+).

Workup

  1. filtrationThe reaction mixture was filtered through Celite®
  2. customthe reaction
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customchromatographed over silica gel (20 g)
  5. washeluting with a gradient of 1-5% CH3CN/CHCl3

Sources & evidence

ORD record
ord-7a535fbe68de4a379d6d86f25e9d1fa3
Source dataset
uspto-grants-1999_09
Patent number
US05952324

Reaction notes

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