1-Chloroethyl chloroformate → HCID 9806285, compound

HRID 1276294Notes

Reaction equation

HRID 1276294 reaction equation
C[N:2]1[CH2:7][CH2:6][C:5]2([C:18]3[C:10](=[CH:11][C:12]4[CH2:13][CH2:14][N:15]([C:19](=[O:39])[C:20]5[CH:25]=[CH:24][C:23]([C:26]6[C:27]([CH3:38])=[N:28][C:29]([N:32]7[CH2:36][CH2:35][CH2:34][C:33]7=[O:37])=[CH:30][CH:31]=6)=[CH:22][CH:21]=5)[C:16]=4[CH:17]=3)[O:9][CH2:8]2)[CH2:4][CH2:3]1.ClC(OC(Cl)C)=O>ClCCCl>[CH3:38][C:27]1[C:26]([C:23]2[CH:22]=[CH:21][C:20]([C:19]([N:15]3[C:16]4[CH:17]=[C:18]5[C:5]6([CH2:8][O:9][C:10]5=[CH:11][C:12]=4[CH2:13][CH2:14]3)[CH2:6][CH2:7][NH:2][CH2:3][CH2:4]6)=[O:39])=[CH:25][CH:24]=2)=[CH:31][CH:30]=[C:29]([N:32]2[CH2:36][CH2:35][CH2:34][C:33]2=[O:37])[N:28]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 22115878HCID 22115878, compound

Product 1

HCID 9806285HCID 9806285, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1'-Methyl-5-[4-(2-methyl-6-(2-oxopyrrolidin-1-yl)pyridin-3-yl]benzoyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (E5, 0.30 g, 0.59 mmol) was stirred under argon in 1,2-dichloroethane (20 ml) with dilsopropylethylamine (0.15 ml, 0.89 mmol) and 1-chloroethyl chloroformate (0.16 ml, 1.5 mmol) for 16 h. The mixture was concentrated in vacuo, and the residue was heated at reflux in methanol (100 ml) for 1.5 h. The solution was evaporated to dryness, and this residue was dissolved in dichloromethane, washed with 10% Na2CO3, dried (Na2SO4) and evaporated to dryness. The material was purified by conversion to the N-t-butoxycarbonyl derivative (di-t-butyldicarbonate, CH2Cl2, 1h), chromatography, and deprotection with trifluoroacetic acid to afford the title compound. The hydrochloride salt was formed by dissolution in dichloromethane, treatment with 1 M HCl in Et2O, and trituration in acetone. This gave 0. 123 g, 39% of a white powder.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. temperaturethe residue was heated
  3. temperatureat reflux in methanol (100 ml) for 1.5 h
  4. customThe solution was evaporated to dryness
  5. dissolutionthis residue was dissolved in dichloromethane
  6. washwashed with 10% Na2CO3
  7. dry with materialdried (Na2SO4)
  8. customevaporated to dryness
  9. customThe material was purified by conversion to the N-t-butoxycarbonyl derivative (di-t-butyldicarbonate, CH2Cl2, 1h), chromatography, and deprotection with trifluoroacetic acid

Sources & evidence

ORD record
ord-66d9fed341684850914966bf4089c366
Source dataset
uspto-grants-2000_12
Patent number
US06166034

Reaction notes

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