Morpholine → 2(R)-benzyloxycarbonylamino-3-(morpholin-4-sulfonyl)propionic acid benzyl ester

HRID 1696058Notes

Reaction equation

HRID 1696058 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.[CH2:16]([O:23][C:24](=[O:42])[CH:25]([NH:31][C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33])[CH2:26][S:27](Cl)(=[O:29])=[O:28])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(#N)C.C(Cl)Cl>[CH2:16]([O:23][C:24](=[O:42])[C@@H:25]([NH:31][C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33])[CH2:26][S:27]([N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)(=[O:29])=[O:28])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 866343682-Benzyloxycarbonylamino-3-chlorosulfonylpropionic acid benzyl ester

Product 1

HCID 672778622(R)-benzyloxycarbonylamino-3-(morpholin-4-sulfonyl)propionic acid benzyl esterYield 99.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of morpholine (Aldrich, 1.27 mL, 14.6 mmol) and N,N-diisopropyl-N-ethylamine (DIPEA, Aldrich, 2.5 mL, 14.6 mmol) in acetonitrile (25 mL) at rt is added solid 2-benzyloxycarbonylamino-3-chlorosulfonylpropionic acid benzyl ester (3.0 g, 7.3 mmol), (prepared as described in Ross, D. L.; Skinner, C. G.; Shive, W. J. Org. Chem. 1959, 24, 1372-1374; and b) Byrnes, S.; Burckart, G. J.; Mokotoff, M. J. Med. Chem. 1978, 21, 45-49], in small portions over 10 min. A clear colorless solution resulted from which white solid began to precipitate within minutes. After 10 min, a thick white suspension was formed. The reaction was diluted in CH2Cl2 to redissolve all solids and the solution washed with 1M HCl. The aqueous layer was separated and extracted with additional CH2Cl2. The organic layer was washed with brine and dried over anhydrous Na2SO4. Following concentration in vacuo, 3.35 g (99%) of 2(R)-benzyloxycarbonylamino-3-(morpholin-4-sulfonyl)propionic acid benzyl ester was obtained as a white solid.

Workup

  1. customA clear colorless solution resulted from which white solid
  2. customto precipitate within minutes
  3. waitAfter 10 min
  4. customa thick white suspension was formed
  5. dissolutionto redissolve all solids
  6. washthe solution washed with 1M HCl
  7. customThe aqueous layer was separated
  8. extractionextracted with additional CH2Cl2
  9. washThe organic layer was washed with brine
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentration in vacuo

Sources & evidence

ORD record
ord-eb3a472a4c4b435cb2c13994e4415a4b
Source dataset
uspto-grants-2012_04
Patent number
US08163735B2

Reaction notes

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