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

HRID 1445425Notes

Reaction equation

HRID 1445425 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.[CH2:40]([NH:47][CH2:48][C:49]1[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[CH:51][CH:50]=1)[CH2:41][CH2:42][CH2:43][CH2:44][CH:45]=[CH2:46]>C1COCC1>[CH2:1]([O:3][C:4]([C:6]1([NH:11][C:12]([CH:14]2[N:18]([C:31](=[O:34])[N:47]([CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH:45]=[CH2:46])[CH2:48][C:49]3[CH:54]=[CH:53][C:52]([O:55][CH3:56])=[CH:51][CH:50]=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

6

Reactant 4

HCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 57956448Hept-6-enyl-(4-methoxy-benzyl)-amineHCID 668708334-Nitro-benzoic acid 5-(1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-pyrrolidin-3-yl ester

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 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Compound 131 (4.68 g, 11.2 mmol) was dissolved in THF (100 ml), NaHCO3 (s) (appr. 5 ml) was added followed by phosgene-solution (20% in toluene, 11.6 ml, 22.5 mmol). The reaction mixture was stirred vigorously for 1 h and then filtrated, evaporated and redissolved in DCM (100 ml). NaHCO3 (s) (appr. 5 ml) was added followed by hept-6-enyl-(4-methoxy-benzyl)-amin (3.92 g, 16.8 mmol). The reaction mixture was stirred at room temperature overnight, filtrated and evaporated on silica. The crude product was purified by column chromatography on silica (EtOAc/n-Heptane 25/75) to give the title compound (6.9 g, 91%).

Workup

  1. filtrationfiltrated
  2. customevaporated
  3. dissolutionredissolved in DCM (100 ml)
  4. additionNaHCO3 (s) (appr. 5 ml) was added
  5. stirringThe reaction mixture was stirred at room temperature overnight
  6. filtrationfiltrated
  7. customevaporated on silica
  8. customThe crude product was purified by column chromatography on silica (EtOAc/n-Heptane 25/75)

Sources & evidence

ORD record
ord-460f55f77c08428dbe183db1dee12b6f
Source dataset
uspto-grants-2010_02
Patent number
US07666834B2

Reaction notes

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