Hydrochloric Acid → [3-(1-Biphenyl-4-ylcyclopropyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl]methanol

HRID 1423973Notes

Reaction equation

HRID 1423973 reaction equation
[C:1]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:6]=[CH:5][C:4]([C:7]2([C:10]3[N:14]4[CH2:15][CH2:16][S:17][C:18]([CH2:21][O:22][Si](C(C)(C)C)(C)C)([CH3:20])[CH2:19][C:13]4=[N:12][N:11]=3)[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.Cl>CO>[C:1]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:2]=[CH:3][C:4]([C:7]2([C:10]3[N:14]4[CH2:15][CH2:16][S:17][C:18]([CH2:21][OH:22])([CH3:20])[CH2:19][C:13]4=[N:12][N:11]=3)[CH2:8][CH2:9]2)=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 867128353-(1-Biphenyl-4-ylcyclopropyl)-8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

Product 1

HCID 71466013[3-(1-Biphenyl-4-ylcyclopropyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl]methanolYield 91%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of the compound (197 mg, 0.39 mmol) obtained in Example 1-3) and 4 M hydrochloric acid (1,4-dioxane solution, 0.5 mL) in methanol (2 mL) was stirred at room temperature for 21 h. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate was added to the residue, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 30:70, gradient) to obtain the title compound (138 mg, 91%) as a colorless solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate
  2. additionwas added to the residue
  3. extractionthe mixture was extracted with dichloromethane
  4. washthe organic layer was washed with saturated sodium chloride solution
  5. dry with materialdried with anhydrous sodium sulfate
  6. filtrationAfter filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 30:70, gradient)

Sources & evidence

ORD record
ord-9a4b6f441fe04c0b83beebb703a667e9
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

Loading…