Acetic Anhydride → HCID 67809686, compound

HRID 1939173Notes

Reaction equation

HRID 1939173 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]([NH:13][CH:14]1[C:20](=[O:21])[N:19]([CH3:22])[C:18]2[CH:23]=[CH:24][CH:25]=[CH:26][C:17]=2[C:16](=[O:27])[CH2:15]1)=[O:12].[BH4-].[Na+].[C:30](OC(=O)C)(=[O:32])[CH3:31].C(N(CC)CC)C>CCO.C1COCC1.CCOC(C)=O.CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:22][N:19]1[C:18]2[CH:23]=[CH:24][CH:25]=[CH:26][C:17]=2[C:16]([O:27][C:30](=[O:32])[CH3:31])=[CH:15][CH:14]([NH:13][C:11](=[O:12])[CH2:10][CH2:9][C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])[C:20]1=[O:21]

Participants

10

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 9909216HCID 9909216, compound

Product 1

HCID 67809686HCID 67809686, compoundYield 33.7%

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of 3-(2,4-Dichloro-phenyl)-N-(1-methyl-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl)-propionamide (3.7 mmol, 1.5 g) in 15 ml EtOH and 5 ml THF was added NaBH4 (3.7 mmol, 0.14 g). This was stirred at rt for 1 h. The reaction was then diluted with 200 ml EtOAc and extracted with 2×100 ml 1N HCl. The organic layer was dried with brine and evaporated under vacuum to 1.4 g of a white powder. The solid was carried on without further purification. To a stirred suspension of the above alcohol in 4 ml CH2Cl2 was added acetic anhydride (0.73 mmol, 75 mg, 0.07 ml), triethyl amine (0.73 mmol, 74 mg, 0.10 ml), 4-dimethylaminopyridine (0.098 mmol,11.9 mg) and the reaction was stirred at rt. The reaction mixture was then diluted with 25 ml CH2Cl2 and extracted with 25 ml H2O, 25 ml saturated NaHCO3. The organic phase was dried with brine and evaporated to a colorless oil. The resulting oil was chromatographed over silica, eluting with 20% to 50% EtOAc:Hex. The pure fractions were collected, evaporated under vacuum, taken up in CH2Cl2 and allowed to evaporate to dryness overnight, resulting in 110 mg of a white solid. mp 142°-144° C.

Workup

  1. extractionextracted with 2×100 ml 1N HCl
  2. dry with materialThe organic layer was dried with brine
  3. customevaporated under vacuum to 1.4 g of a white powder
  4. customThe solid was carried on without further purification
  5. additionTo a stirred suspension of the above alcohol in 4 ml CH2Cl2
  6. stirringthe reaction was stirred at rt
  7. extractionextracted with 25 ml H2O, 25 ml saturated NaHCO3
  8. dry with materialThe organic phase was dried with brine
  9. customevaporated to a colorless oil
  10. customThe resulting oil was chromatographed over silica
  11. washeluting with 20% to 50% EtOAc
  12. customThe pure fractions were collected
  13. customevaporated under vacuum
  14. customto evaporate to dryness overnight

Sources & evidence

ORD record
ord-15442eba6b594f2f9cbf9c162ede4db3
Source dataset
uspto-grants-1997_12
Patent number
US05696111

Reaction notes

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