Acetic Acid → 1-(1-Boc-4-piperidyl)-4-methyl-3,1-benzoxazin-2-one

HRID 2414328Notes

Reaction equation

HRID 2414328 reaction equation
[C:1]([OH:4])(=[O:3])C.[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6].[NH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH:26](O)[CH3:27].C([BH3-])#N.[Na+]>ClCCl>[CH3:27][CH:26]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[N:19]([CH:15]2[CH2:16][CH2:17][N:12]([C:10]([O:9][C:5]([CH3:8])([CH3:7])[CH3:6])=[O:11])[CH2:13][CH2:14]2)[C:1](=[O:3])[O:4]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1120582-Amino-alpha-methylbenzenemethanolHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 229147301-(1-Boc-4-piperidyl)-4-methyl-3,1-benzoxazin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Acetic acid (1 ml) was added dropwise to a solution of N-tert-butoxycarbonyl-4-piperidone (9.4 g), 1-(2-amino-phenyl)-ethanol (4.3 g) and sodium cyanoborohydride (10 g) in dichloromethane and the mixture stirred at room temperature overnight. The mixture was partitioned between ethyl acetate and water, the organics separated and washed with aqueous sodium hydrogencarbonate solution, water, dried, and evaporated under reduced pressure. The crude product was dissolved in tetrahydrofuran (100 ml) and N,N-diisopropylethylamine (23 ml), cooled to 0° C., then triphosgene (4.3 g) added. The mixture was warmed to room temperature and stirred overnight. The mixture was partitioned between ethyl acetate and water, the organics washed with water, dried and evaporated under reduced pressure. Purification was by chromatography eluting with 20% ethyl acetate/isohexane. Yield 1.4 g.

Workup

  1. customThe mixture was partitioned between ethyl acetate and water
  2. customthe organics separated
  3. washwashed with aqueous sodium hydrogencarbonate solution, water
  4. customdried
  5. customevaporated under reduced pressure
  6. dissolutionThe crude product was dissolved in tetrahydrofuran (100 ml)
  7. temperatureN,N-diisopropylethylamine (23 ml), cooled to 0° C.
  8. additiontriphosgene (4.3 g) added
  9. temperatureThe mixture was warmed to room temperature
  10. stirringstirred overnight
  11. customThe mixture was partitioned between ethyl acetate and water
  12. washthe organics washed with water
  13. customdried
  14. customevaporated under reduced pressure
  15. customPurification
  16. washeluting with 20% ethyl acetate/isohexane

Sources & evidence

ORD record
ord-83ad2b2942844498a9bea4f179c1ca74
Source dataset
uspto-grants-2004_11
Patent number
US06812226B2

Reaction notes

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