Benzyl chloroformate → (3R,4S)-tert-butyl 4-(((benzyloxy)carbonyl)amino)-3-fluoropiperidine-1-carboxylate

HRID 339705Notes

Reaction equation

HRID 339705 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C@H:3]1[F:15].C([O-])([O-])=O.[K+].[K+].Cl[C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24]>C1COCC1.O.CCOC(C)=O>[CH2:26]([O:25][C:23]([NH:1][C@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])[CH2:4][C@H:3]1[F:15])=[O:24])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

7

Reactant 3

HCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 112644351,1-Dimethylethyl (3R,4S)-4-amino-3-fluoro-1-piperidinecarboxylate

Product 1

HCID 86708534(3R,4S)-tert-butyl 4-(((benzyloxy)carbonyl)amino)-3-fluoropiperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product from Step D (10 g, 45.8 mmol) in THF (90 mL) and water (20 mL) was added K2CO3 (8.23 g, 59.6 mmol). Once the solid was dissolved benzyl chloroformate (7.19 mL, 50.4 mmol) was added. The reaction was stirred vigorously at ambient temperature for 5.0 hours. Once the reaction was complete by TLC the reaction was diluted with EtOAc (100 mL) and water (20 mL). The layers were separated and the organic layer was washed with brine, then dried over Na2SO4, filtered and concentrated in vacuo. The product was purified by column chromatography (EtOAc/hexane) to afford 12.9 g (80%) of a sticky, white foam.

Workup

  1. additionwas added
  2. customThe layers were separated
  3. washthe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe product was purified by column chromatography (EtOAc/hexane)
  8. customto afford 12.9 g (80%) of a sticky, white foam

Sources & evidence

ORD record
ord-60edf854f76141f49c5a348e8bb77f23
Source dataset
uspto-grants-2014_11
Patent number
US08895550B2

Reaction notes

Loading…