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

HRID 1424000Notes

Reaction equation

HRID 1424000 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]3[N:15]4[CH2:16][CH2:17][S:18][C:19]([CH2:22][O:23][Si](C(C)(C)C)(C)C)([CH3:21])[CH2:20][C:14]4=[N:13][N:12]=3)[CH2:10][CH2:9]2)=[C:4]([F:31])[CH:3]=1.Cl>CO>[F:31][C:4]1[CH:3]=[C:2]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:7]=[CH:6][C:5]=1[C:8]1([C:11]2[N:15]3[CH2:16][CH2:17][S:18][C:19]([CH2:22][OH:23])([CH3:21])[CH2:20][C:14]3=[N:13][N:12]=2)[CH2:9][CH2:10]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 867128533-[1-(4-Bromo-2-fluorophenyl)cyclopropyl]-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 86712854{3-[1-(3-Fluorobiphenyl-4-yl)cyclopropyl]-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl}methanolYield 218.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of the compound (191 mg, 0.36 mmol) obtained in Example 14-6) and 4 M hydrochloric acid (1,4-dioxane solution, 2 mL) in methanol (3 mL) was stirred at room temperature for 14 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 40:60, gradient) to obtain the title compound (161 mg, quant.) 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 40:60, gradient)

Sources & evidence

ORD record
ord-d24f74c77fe0460db9fc7136f813f077
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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