Ethyl Acetate → hexahydro-1-(1,2,3,4-tetrahydrobenzo[b]thieno[2,3-c]pyridine-3-carbonyl)-1H-1,4-diazepine

HRID 893856Notes

Reaction equation

HRID 893856 reaction equation
C(OC([CH:8]1[S:20][C:11]23[CH:19]=[CH:18][CH:17]=[CH:16][C:12]2=[N:13][CH2:14][CH2:15][CH:10]3[CH:9]1[C:21]([OH:23])=O)=O)(C)(C)C.[NH:24]1[CH2:30][CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(OCC)(=O)C>CN(C)C=O.O>[S:20]1[C:11]23[CH:19]=[CH:18][CH:17]=[CH:16][C:12]2=[N:13][CH2:14][CH2:15][CH:10]3[CH:9]([C:21]([N:24]2[CH2:30][CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[O:23])[CH2:8]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 68163Hexahydro-1,4-diazepineHCID 199401P,P-Diphenylphosphinic azideHCID 699596062-Tert-butoxycarbonyl-1,2,3,4-tetrahydro-benzo[b]thieno[2,3-c]pyridine-3-carboxylic acid

Product 1

HCID 69959846hexahydro-1-(1,2,3,4-tetrahydrobenzo[b]thieno[2,3-c]pyridine-3-carbonyl)-1H-1,4-diazepineYield 79.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
50 °C

Procedure

In 5 ml of dimethylformamide were dissolved 0.32 g of 2-tert-butoxycarbonyl-1,2,3,4-tetrahydrobenzo[b]thieno[2,3-c]pyridine-3-carboxylic acid and 0.2 g of hexahydro-1H-1,4-diazepine and after adding thereto 3 ml of a dimethylformamide solution of 0.33 g of diphenylphosphorylazide, the mixture was stirred overnight. To the reaction mixture was added 50 g of ethyl acetate and the mixture was washed twice with an aqueous 5% sodium hydrogencarbonate solution and then twice with a saturated sodium chloride solution, and thereafter dried with sodium sulfate. After filtering away sodium sulfate, 5 ml of a mixture of 1N hydrochloric acid in ethyl acetate were added to the filtrate and the mixture was heated to 50° C. for one hours. After distilling off ethyl acetate under reduced pressure, the residue formed was dissolved in 30 ml of water and the solution was washed thrice with 10 ml of ethyl ether. The aqueous layer was adjusted to pH 12 with an aqueous solution of 5N sodium hydroxide and after adding thereto 1 g of sodium chloride, the reaction mixture was extracted thrice with chloroform. The chloroform layer was dried by magnesium sulfate and then the residue formed was purified by silica gel thin layer chromatography (solvent: ethyl acetate and methanol of 10:1). Then, 2 ml of a mixture of 1N hydrochloric acid in ethyl acetate was added to the product and crystals thus deposited were collected by filtration to provide 0.24 g (yield of 62%) of hexahydro-1-(1,2,3,4-tetrahydrobenzo[b]thieno[2,3-c]pyridine-3-carbonyl)-1H-1,4-diazepine.di-hydrochloride. (See Table 9-1, Table 10-1).

Workup

  1. additionafter adding
  2. washthe mixture was washed twice with an aqueous 5% sodium hydrogencarbonate solution
  3. dry with materialtwice with a saturated sodium chloride solution, and thereafter dried with sodium sulfate
  4. filtrationAfter filtering away sodium sulfate, 5 ml of a mixture of 1N hydrochloric acid in ethyl acetate
  5. additionwere added to the filtrate
  6. distillationAfter distilling off ethyl acetate under reduced pressure
  7. customthe residue formed
  8. washthe solution was washed thrice with 10 ml of ethyl ether
  9. additionafter adding
  10. extraction1 g of sodium chloride, the reaction mixture was extracted thrice with chloroform
  11. dry with materialThe chloroform layer was dried by magnesium sulfate
  12. customthe residue formed
  13. customwas purified by silica gel thin layer chromatography (solvent: ethyl acetate and methanol of 10:1)
  14. additionThen, 2 ml of a mixture of 1N hydrochloric acid in ethyl acetate was added to the product and crystals
  15. filtrationthus deposited were collected by filtration

Sources & evidence

ORD record
ord-234288e0bb7a4d89be713cc568aacb53
Source dataset
uspto-grants-1992_06
Patent number
US05126448

Reaction notes

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