Benzyl chloroformate → Benzyl (3-fluoropiperidin-4-yl)carbamate

HRID 970379Notes

Reaction equation

HRID 970379 reaction equation
C([NH:8][C@H:9]1[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][C@H:10]1[F:22])C1C=CC=CC=1.Cl[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25]>C(O)C.[OH-].[OH-].[Pd+2]>[CH2:27]([O:26][C:24]([NH:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH:10]1[F:22])=[O:25])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 2

HCID 10387Benzyl chloroformateHCID 11312869cis-4-Benzylamino-1-tert-butoxycarbonyl-3-fluoropiperidine

Product 1

HCID 21948945Benzyl (3-fluoropiperidin-4-yl)carbamateYield 98%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Procedure

cis-(+)-4-Benzylamino-1-tert-butoxycarbonyl-3-fluoropiperidine [Enantiomer 1] (15.0 g, 0.049 mole) in ethanol (300 ml) was hydrogenated over 20% palladium hydroxide on carbon (4 g) at 30 psi for 5 h, then filtered through celite and evaporated. The crude amine was dissolved in ethyl acetate (100 mL), saturated sodium hydrogen carbonate solution (100 mL) was added followed by benzyl chloroformate (7.6 mL, 0.53 mole) and the mixture stirred vigorously for 4 h. The organic phase was separated dried and evaporated. The product was dissolved in DCM (75 mL) and stirred with TFA (20 mL) for 4 h then evaporated. The residue was basified with sodium carbonate solution, extracted with 10% methanol in DCM and the extracts dried and evaporated to give a white solid (12.1 g, 98%), [α]D+61.10 (MeOH).

Workup

  1. filtrationfiltered through celite
  2. customevaporated
  3. dissolutionThe crude amine was dissolved in ethyl acetate (100 mL)
  4. additionsaturated sodium hydrogen carbonate solution (100 mL) was added
  5. customThe organic phase was separated
  6. customdried
  7. customevaporated
  8. dissolutionThe product was dissolved in DCM (75 mL)
  9. stirringstirred with TFA (20 mL) for 4 h
  10. customthen evaporated
  11. extractionextracted with 10% methanol in DCM
  12. customthe extracts dried
  13. customevaporated

Sources & evidence

ORD record
ord-3f93811877c04631998a52e2bd240f88
Source dataset
uspto-grants-2007_12
Patent number
US07312212B2

Reaction notes

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