Sodium hydride → (4aR*,8aR*)-2-oxo-octahydro-pyrido[3,4-b][1,4]oxazine-6-carboxylic acid tert-butyl ester

HRID 2066542Notes

Reaction equation

HRID 2066542 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([NH:14][C:15](=[O:18])[CH2:16]Cl)[C@H:10]([OH:19])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]2[C@H:10]([O:19][CH2:16][C:15](=[O:18])[NH:14]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 58745622(3R*,4R*)-4-(2-chloro-acetylamino)-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 58745484(4aR*,8aR*)-2-oxo-octahydro-pyrido[3,4-b][1,4]oxazine-6-carboxylic acid tert-butyl esterYield 55.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of (3R*,4R*)-4-(2-chloro-acetylamino)-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (2.70 g, 9.23 mmol) in tetrahydrofuran (30 mL) cooled down to 0° C. was added sodium hydride, 60% dispersion in mineral oil (830 mg, 1.1 eq) portionwise. The mixture was warmed to room temperature and stirred for 6 hours. The mixture was partitioned between dichloromethane and brine. The combined organic layers were washed with brine, separated and dried (MgSO4). The crude product was purified by column chromatography to yield (4aR*,8aR*)-2-oxo-octahydro-pyrido[3,4-b][1,4]oxazine-6-carboxylic acid tert-butyl ester (1.31 g).

Workup

  1. customThe mixture was partitioned between dichloromethane and brine
  2. washThe combined organic layers were washed with brine
  3. customseparated
  4. dry with materialdried (MgSO4)
  5. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-82c11d40ea6c4ab69a01843698f665a5
Source dataset
uspto-grants-2012_10
Patent number
US08293735B2

Reaction notes

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