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

HRID 579668Notes

Reaction equation

HRID 579668 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 (160 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-839953a91f7343c3906630d849116de8
Source dataset
uspto-grants-2015_05
Patent number
US09040562B2

Reaction notes

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