4-Methylmorpholine → (1S)-[1-Hydroxymethyl-3-(tritylcarbamoyl)propyl]carbamic Acid Benzyl Ester

HRID 1057748Notes

Reaction equation

HRID 1057748 reaction equation
CN1CCOCC1.ClC(OCC)=O.[NH:14]([C:43]([O:45][CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:44])[C@H:15]([C:40](O)=[O:41])[CH2:16][CH2:17][C:18](=[O:39])[NH:19][C:20]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[BH4-].[Na+]>C1COCC1.O>[CH2:46]([O:45][C:43](=[O:44])[NH:14][C@H:15]([CH2:40][OH:41])[CH2:16][CH2:17][C:18](=[O:39])[NH:19][C:20]([C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 10962399Z-Gln(Trt)-OH

Product 1

HCID 10505827(1S)-[1-Hydroxymethyl-3-(tritylcarbamoyl)propyl]carbamic Acid Benzyl Ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

4-Methylmorpholine (1.89 mL, 17.2 mmol, 1 equiv) and ethyl chloroformate (1.65 mL, 17.3 mmol, 1 equiv) were added to a mixture of commercially available Cbz-Gln(Trt)-OH (9.00 g, 17.2 mmol, 1 equiv) in THF (23 mL) at −10° C. After stirring 20 min, the reaction mixture was filtered and the filtrate was added dropwise to a suspension of NaBH4 (1.47 g, 38.9 mmol, 2.25 equiv) in H2O (10 mL) at 0° C. The resulting mixture was allowed to warm to 23° C. and stirred for 5 h. It was then cooled again to 0° C., quenched by the careful addition of 1 N HCl (30 mL) and then partitioned between MTBE (500 mL) and brine (2×100 mL). The organic phase was dried over Na2SO4 and evaporated to provide the title intermediate which was used without further purification.

Workup

  1. filtrationthe reaction mixture was filtered
  2. stirringstirred for 5 h
  3. temperatureIt was then cooled again to 0° C.
  4. customquenched by the careful addition of 1 N HCl (30 mL)
  5. custompartitioned between MTBE (500 mL) and brine (2×100 mL)
  6. dry with materialThe organic phase was dried over Na2SO4
  7. customevaporated

Sources & evidence

ORD record
ord-922dbb5c2c104c169669214862f2bb92
Source dataset
uspto-grants-2003_02
Patent number
US06514997B2

Reaction notes

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