Tetrahydrofuran → 3-Diphenylmethoxycarbonyl-1-(2-benzyloxycarbonylamino-4-thiazolyl)-2-propene-1,1-dicarboxylic acid diethyl ester

HRID 1906538Notes

Reaction equation

HRID 1906538 reaction equation
[CH2:1]([O:3][C:4](=[O:27])[CH:5]([C:11]1[N:12]=[C:13]([NH:16][C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[S:14][CH:15]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].[H-].[Na+].Cl/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34].O1[CH2:40][CH2:39][CH2:38][CH2:37]1>C(OCC)(=O)C.Cl>[CH2:9]([O:8][C:6]([C:5]([C:11]1[N:12]=[C:13]([NH:16][C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[S:14][CH:15]=1)([C:4]([O:3][CH2:1][CH3:2])=[O:27])[CH:31]=[CH:32][C:33]([O:35][CH:37]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:38]1[CH:6]=[CH:5][CH:4]=[CH:40][CH:39]=1)=[O:34])=[O:7])[CH3:10]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 638124trans-3-Chloroacrylic acidHCID 136714242-(2-Benzyloxycarbonylamino-4-thiazolyl)malonic acid diethyl ester

Product 1

HCID 541243823-Diphenylmethoxycarbonyl-1-(2-benzyloxycarbonylamino-4-thiazolyl)-2-propene-1,1-dicarboxylic acid diethyl ester

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(2-benzyloxycarbonylamino-4-thiazolyl)malonic acid diethyl ester in tetrahydrofuran (20 parts) are added sodium hydride (2.35 equivalents) and a solution of trans-3-chloroacrylic acid diphemylmethyl ester (1.2 equivalents) in tetrahydrofuran (8 parts) under ice cooling. After stirring at 35° to 40° C. for 12.5 hours, the mixture is diluted with ethyl acetate and diluted hydrochloric acid, washed with water, dried, and concentrated. The residue is chromatographed over silica gel. The fraction eluted with a mixture of benzene and ethyl acetate (15:1) is crystallized from ethyl acetate to give 3-diphenylmethoxycarbonyl-1-(2-benzyloxycarbonylamino-4-thiazolyl)-2-propene-1,1-dicarboxylic acid diethyl ester.

Workup

  1. washwashed with water
  2. customdried
  3. concentrationconcentrated
  4. customThe residue is chromatographed over silica gel
  5. washThe fraction eluted with a mixture of benzene and ethyl acetate (15:1)
  6. customis crystallized from ethyl acetate

Sources & evidence

ORD record
ord-b2a4fb4ac36a474cb71c797adfe8b550
Source dataset
uspto-grants-1987_03
Patent number
US04652652

Reaction notes

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