Benzyl chloroformate → Benzyl [4-(benzyloxy)-3-fluorophenyl]carbamate

HRID 2387571Notes

Reaction equation

HRID 2387571 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][C:10]=1[F:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26].CCCCCC.C(OCC)(=O)C>C(OCC)(=O)C>[CH2:28]([O:27][C:25](=[O:26])[NH:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:10]([F:18])[CH:11]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 10387Benzyl chloroformateHCID 516892Sodium Bicarbonate2×HCID 21226206Ethyl acetate hexaneHCID 220309121-(Benzyloxy)-2-fluoro-4-nitrobenzene

Product 1

HCID 57754845Benzyl [4-(benzyloxy)-3-fluorophenyl]carbamate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

A solution of 34.9 g 1-benzyloxy-2-fluoro-4-nitro-benzene (WO03064413) (MW: 247.28, 141 mmol) and 340 mg platine 5% on activated carbon in 350 ml ethyl acetate was stirred under hydrogen at rt and normal pressure. The reaction was monitored by HPLC and was complete after twenty hours. The catalyst was filtered over a glas fibre filter, and the filtrate evaporated under reduced pressure to dryness. The oily residue was dissolved in 500 ml acetone and treated with 250 ml of a saturated solution of sodium bicarbonate and 17.5 g of sodium bicarbonate (MW: 84.01, 208 mmol). The mixture was cooled to 5° C. and treated drop wise with 26.08 g of benzyl chloroformate (MW: 170.59, 152 mmol). The reaction was allowed to stirred at room temperature for two hours and monitored by TLC (hexane/ethyl acetate 3:1). The acetone was evaporated, the residue diluted with 500 ml water, and the solid filtered off. The crystals were washed with 500 ml water and dried. Yield: 48.05 g, 95.8%. MS: 352.5 (M+H)+, 350.8, (M−H)−. Method ESI+, ESI−.

Workup

  1. waitwas complete after twenty hours
  2. filtrationThe catalyst was filtered over a glas fibre filter
  3. customthe filtrate evaporated under reduced pressure to dryness
  4. dissolutionThe oily residue was dissolved in 500 ml acetone
  5. customThe acetone was evaporated
  6. additionthe residue diluted with 500 ml water
  7. filtrationthe solid filtered off
  8. washThe crystals were washed with 500 ml water
  9. customdried

Sources & evidence

ORD record
ord-a0f0e4de5c254d4bb91449d155707810
Source dataset
uspto-grants-2012_09
Patent number
US08268812B2

Reaction notes

Loading…