Benzyl chloroformate → N-(carbobenzyloxy)-4-[3-[(tert-butyldimethylsilyl)oxy]-1-azetidinyl]-3-fluoroaniline

HRID 1418650Notes

Reaction equation

HRID 1418650 reaction equation
[Si:1]([O:8][CH:9]1[CH2:12][N:11]([C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][C:14]=2[F:22])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H][H].C(=O)(O)[O-].[Na+].Cl[C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32]>[Pd].C(OCC)(=O)C.CCCCCC.O1CCCC1.O>[C:31]([NH:19][C:16]1[CH:17]=[CH:18][C:13]([N:11]2[CH2:12][CH:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:10]2)=[C:14]([F:22])[CH:15]=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 516892Sodium BicarbonateHCID 537387084-[3-[(Tert-butyldimethylsilyl)oxy]-1-azetidinyl]-3-fluoronitrobenzeneHCID 178418361HCID 178418361, compound

Product 1

HCID 70193876N-(carbobenzyloxy)-4-[3-[(tert-butyldimethylsilyl)oxy]-1-azetidinyl]-3-fluoroanilineYield 43%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 21226206Ethyl acetate hexaneSolvent2×HCID 21881883Oxolane--water (1/1)Solvent

Procedure

4-[3-[(tert-Butyldimethylsilyl)oxy]-1-azetidinyl]-3-fluoronitrobenzene (1.00 g, 3.07 mmol) was combined with 10% palladium on carbon (0.100 g) in 3:1 tetrahydrofuran/water (25 mL) under a nitrogen atmosphere. The atmosphere was replaced with hydrogen (balloon) by repeated evacuation and filling. After 2 h the initial yellow color of the reaction solution disappeared and TLC analysis (15% ethyl acetate/hexane) revealed the reduction to be complete. The reaction mixture was filtered through Celite® and the filtrate immediately placed under a nitrogen atmosphere and treated with sodium bicarbonate (1.41 g, 16.8 mmol) and benzyl chloroformate (0.528 mL, 3.69 mmol). After 30 min at ambient temperature, TLC analysis (15% ethyl acetate/hexane) indicated the reaction was complete. The reaction mixture was concentrated under reduced pressure to an off-white solid. Cromatography over silica gel (125 g), eluting with a gradient of 5-30% ethyl acetate/hexane, afforded, after concentration of appropriate fractions, 0.565 g (43%) of the title compound as a white solid with mp 91°-93° C. and MS(EI) 430 (M+).

Workup

  1. filtrationThe reaction mixture was filtered through Celite®
  2. waitAfter 30 min at ambient temperature
  3. concentrationThe reaction mixture was concentrated under reduced pressure to an off-white solid
  4. washCromatography over silica gel (125 g), eluting with a gradient of 5-30% ethyl acetate/hexane
  5. customafforded

Sources & evidence

ORD record
ord-6695130e48c9486d827525408bff7a05
Source dataset
uspto-grants-1999_03
Patent number
US05883093

Reaction notes

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