4-Methylmorpholine → tert-butyl [(1S)-4-[(tert-butoxycarbonyl)amino]-1-(hydroxymethyl)butyl]carbamate

HRID 269611Notes

Reaction equation

HRID 269611 reaction equation
CN1CCOCC1.ClC(OCC)=O.[C:14]([O:18][C:19]([NH:21][C@H:22]([C:34](O)=[O:35])[CH2:23][CH2:24][CH2:25][NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[O:20])([CH3:17])([CH3:16])[CH3:15].[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O1CCCC1.O>[C:14]([O:18][C:19](=[O:20])[NH:21][C@H:22]([CH2:34][OH:35])[CH2:23][CH2:24][CH2:25][NH:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])([CH3:15])([CH3:17])[CH3:16]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 7015803Boc-orn(boc)-OHHCID 21226445Aluminium lithium hydride

Product 1

HCID 86601679tert-butyl [(1S)-4-[(tert-butoxycarbonyl)amino]-1-(hydroxymethyl)butyl]carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

91 mg (0.90 mmol) of 4-methylmorpholine and 98 mg (0.90 mmol) of ethyl chloroformate are added to a solution of 300 mg (0.90 mmol) of N2,N5-bis(tert-butoxycarbonyl)-L-ornithine in 10 ml of tetrahydrofuran at −10° C., and the mixture is stirred for 30 min. At this temperature, 1.81 ml (1.81 mmol) of a 1M solution of lithium aluminum hydride in tetrahydrofuran are slowly added dropwise. The mixture is slowly warmed to RT and stirred at RT for 12 h. While cooling in ice, 0.1 ml of water and 0.15 ml of a 4.5% sodium hydroxide solution are cautiously added, and the mixture is stirred at RT for a further 3 h. The mixture is filtered and the filtrate is concentrated in vacuo. The residue is dissolved in ethyl acetate, washed with water, dried over magnesium sulfate and again evaporated to dryness in vacuo. The product is reacted without further purification.

Workup

  1. stirringstirred at RT for 12 h
  2. temperatureWhile cooling in ice
  3. stirringthe mixture is stirred at RT for a further 3 h
  4. filtrationThe mixture is filtered
  5. concentrationthe filtrate is concentrated in vacuo
  6. dissolutionThe residue is dissolved in ethyl acetate
  7. washwashed with water
  8. dry with materialdried over magnesium sulfate
  9. customagain evaporated to dryness in vacuo
  10. customThe product is reacted without further purification

Sources & evidence

ORD record
ord-7ee5e82a57ec4d5789d59ec3b9ca9c45
Source dataset
uspto-grants-2008_11
Patent number
US07446102B2

Reaction notes

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