N-(benzyloxycarbonyloxy)succinamide → tert-Butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate

HRID 857262

Reaction equation

HRID 857262 reaction equation
Cl.[CH2:2]([C@H:9]([NH:23][C:24](=[O:33])[O:25]CC1C=CC=CC=1)[C@H:10]([OH:22])[CH2:11][NH:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:34](OC(ONC(=O)CCC(N)=O)=O)[C:35]1[CH:40]=CC=C[CH:36]=1>C1COCC1>[CH2:2]([C@H:9]([NH:23][C:24](=[O:33])[O:25][C:35]([CH3:40])([CH3:36])[CH3:34])[C@H:10]([OH:22])[CH2:11][NH:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 21865880N-(benzyloxycarbonyloxy)succinamideHCID 86617171HCID 86617171, compound

Product 1

HCID 57512771tert-Butyl (1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl (1S, 2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propylcarbamate (VII, PREPARATION 8, 19.2 g, 48 mmole) in THF (100 ml). The reaction mixture is cooled to 0° and treated with N-benzyloxy carbonyloxysuccinamide (11.9 g, 48 mmole) while maintaining temperature <5°. The reaction mixture is stirred overnight and in the morning is concentrated under reduced pressure. The residue is partitioned between ethyl acetate and saturated aqueous bicarbonate. The organic phase is separated and washed with citric acid (5%), saline, dried over sodium sulfate and concentrated. The crude product is purified by preparatory HPLC eluting with a gradient of from 20/80–50/50 ethyl acetate. To give the title compound, M+H=534.

Workup

  1. temperatureThe reaction mixture is cooled to 0°
  2. temperaturewhile maintaining temperature <5°
  3. concentrationis concentrated under reduced pressure
  4. customThe residue is partitioned between ethyl acetate and saturated aqueous bicarbonate
  5. customThe organic phase is separated
  6. washwashed with citric acid (5%), saline
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe crude product is purified by preparatory HPLC
  10. washeluting with a gradient of from 20/80–50/50 ethyl acetate

Sources & evidence

ORD record
ord-ee69ec2539d0460f9ceb3374822ebe74
Source dataset
uspto-grants-2006_12
Patent number
US07144897B2

Linked notes

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