Carbon Dioxide → HCID 54275151, compound

HRID 1378237Notes

Reaction equation

HRID 1378237 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=O)[C@@H:9]3[CH2:13][CH2:14][N:8]3[C:7](=[O:15])[C:6]=2[CH:16]=1.[Li+:17].[CH3:18][CH:19]([N-:21][CH:22]([CH3:24])[CH3:23])[CH3:20].C(NC(C)C)(C)C.P(Cl)(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.[N+:49]([CH2:51][C:52]([O:54][CH2:55][CH3:56])=[O:53])#[C-:50].C(=O)=O.[Cl-].[NH4+]>C1COCC1.CN1C(=O)N(C)CCC1.C1COCC1.C([Li])CCC.CCCCCC>[Li+:17].[CH3:18][CH:19]([N-:21][CH:22]([CH3:24])[CH3:23])[CH3:20].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:50]=[N:49][C:51]([C:52]([O:54][CH2:55][CH3:56])=[O:53])=[C:10]3[C@@H:9]3[CH2:13][CH2:14][N:8]3[C:7](=[O:15])[C:6]=2[CH:16]=1

Participants

13

Reactant 7

HCID 280Carbon DioxideHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 75654Diphenyl chlorophosphateHCID 533707Ethyl isocyanoacetate2×HCID 2724682Lithium diisopropylamideHCID 54138438HCID 54138438, compound

Product 2

HCID 2724682Lithium diisopropylamideHCID 54275151HCID 54275151, compoundYield 54%

Reagents, catalysts & solvents 4

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 22565281tetrahydrofuran 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinoneSolvent2×HCID 178418339ButyllithiumSolvent

Procedure

23.6 g (0.1 mol) of (S)-6-chloro-1,2,4,9,10,10a-hexahydro-azeto[2,1-c][1,4]benzodiazepine-4,10-dione in 300 ml of THF/DMPU 5:1 were added dropwise under argon at about -75° to a LDA solution (prepared in the usual manner from 16 ml (0.11 mol) of diisopropylamine in 200 ml of THF and 69 ml of 1.6M n-butyllithium solution in hexane). The mixture was stirred for a further 40 min. 23 ml (0.11 mol) of diphenyl chlorophosphate were added dropwise thereto at about -75° and the mixture was stirred at -75° for 35 min. In the meanwhile and separately, a further LDA solution was prepared as described above (100 ml of THF). Thereto there was now added dropwise at about -75° a solution of 12.0 ml (0.11 mol) of ethyl isocyano- acetate in 20 ml of THF/DMPU 1:1. The deprotonized ethyl isocyanoacetate was added dropwise at about -70° via a dropping funnel cooled with dry ice within 30 min. to the initially described reaction mixture. The mixture was stirred in an acetone/dry-ice bath for 2 hrs, 100 ml of 20% ammonium chloride solution were added at <-60° and the mixture was poured into 800 ml of ice-water. The mixture was extracted three times with 200 ml of methylene chloride, dried with sodium sulfate and evaporated. The brown oil was dissolved in 300 ml of ethyl acetate, whereupon 300 ml of n-hexane were added slowly. The crystals were filtered off. Further product was obtained by chromatography of the mother liquor on 300 g of silica gel (methylene chloride/acetone 9:1). After drying in a vacuum there were obtained 17.8 g (54%) of ethyl (S)-7-chloro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxylate of m.p. 190°-194° (ethyl acetate).

Workup

  1. stirringat about -75° and the mixture was stirred at -75° for 35 min
  2. stirringThe mixture was stirred in an acetone/dry-ice bath for 2 hrs
  3. extractionThe mixture was extracted three times with 200 ml of methylene chloride
  4. dry with materialdried with sodium sulfate
  5. customevaporated
  6. dissolutionThe brown oil was dissolved in 300 ml of ethyl acetate, whereupon 300 ml of n-hexane
  7. additionwere added slowly
  8. filtrationThe crystals were filtered off
  9. customFurther product was obtained by chromatography of the mother liquor on 300 g of silica gel (methylene chloride/acetone 9:1)
  10. customAfter drying in a vacuum there

Sources & evidence

ORD record
ord-cea394bcfcec412caab94ee61f297aee
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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