Toluene → 4-Nitro-benzoic acid 5-(1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-1-[hept-6-enyl-(4-methoxy-benzyl)-carbamoyl]-pyrrolidin-3-yl ester

HRID 1692498Notes

Reaction equation

HRID 1692498 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[NH:18][CH2:17][CH:16]([O:19][C:20](=[O:30])[C:21]3[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=3)[CH2:15]2)=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2].[C:31]([O-:34])(O)=O.[Na+].C(Cl)(Cl)=O.C1(C)C=CC=CC=1.[CH2:47]([NH:54][CH2:55][C:56]1[CH:61]=[CH:60][C:59]([O:62][CH3:63])=[CH:58][CH:57]=1)[CH2:48][CH2:49][CH2:50][CH:51]=[CH:52][CH3:53]>C1COCC1>[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[N:18]([C:31](=[O:34])[N:54]([CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH:52]=[CH2:53])[CH2:55][C:56]3[CH:61]=[CH:60][C:59]([O:62][CH3:63])=[CH:58][CH:57]=3)[CH2:17][CH:16]([O:19][C:20](=[O:30])[C:21]3[CH:22]=[CH:23][C:24]([N+:27]([O-:29])=[O:28])=[CH:25][CH:26]=3)[CH2:15]2)=[O:13])[CH2:8][CH:7]1[CH:9]=[CH2:10])=[O:5])[CH3:2]

Participants

7

Reactant 5

HCID 1140TolueneHCID 6371PhosgeneHCID 516892Sodium Bicarbonate2×HCID 668708334-Nitro-benzoic acid 5-(1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-pyrrolidin-3-yl esterHCID 66871144Hept-5-enyl-(p-methoxybenzyl)-amine

Product 1

HCID 668705064-Nitro-benzoic acid 5-(1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-1-[hept-6-enyl-(4-methoxy-benzyl)-carbamoyl]-pyrrolidin-3-yl esterYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of compound 134 (4.5 g, 10.8 mmol) in THF (1.60 mL) were added NaHCO3 (1 tablespoon) and phosgene in toluene (1.93 M, 11.5 mL, 22 mmol). The mixture was vigorously stirred for 1 h at room temperature, and then filtered and evaporated. The residue was dissolved in CH2Cl2 (160 mL), and NaHCO3 (1 tablespoon) and hept-5-enyl-(p-methoxybenzyl)-amine (4.3 g, 18.5 mmol) were added. After stirring overnight at room temperature the reaction mixture was filtered and evaporated to dryness. Flash column chromatography on silica gel (EtOAc:toluene 25:75→40:60) gave the title compound (6.59 g, 90%) as a light brown syrup.

Workup

  1. filtrationfiltered
  2. customevaporated
  3. dissolutionThe residue was dissolved in CH2Cl2 (160 mL)
  4. stirringAfter stirring overnight at room temperature the reaction mixture
  5. filtrationwas filtered
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-22083fd5ebae40e3bf0a40cd324724ec
Source dataset
uspto-grants-2012_04
Patent number
US08153800B2

Reaction notes

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