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

HRID 1424133Notes

Reaction equation

HRID 1424133 reaction equation
[Si]([O:8][CH2:9][C@:10]1([CH3:34])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:28]=[CH:27][C:26]([C:29]5[O:30][CH:31]=[CH:32][N:33]=5)=[CH:25][CH:24]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1)(C(C)(C)C)(C)C.Cl>CO>[CH3:34][C@@:10]1([CH2:9][OH:8])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:24]=[CH:25][C:26]([C:29]5[O:30][CH:31]=[CH:32][N:33]=5)=[CH:27][CH:28]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86712977(8R)-8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-{1-[4-(1,3-oxazol-2-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

Product 1

HCID 86712978{(8R)-8-Methyl-3-{1-[4-(1,3-oxazol-2-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepin-8-yl}methanolYield 88.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of the compound (674 mg, 1.36 mmol) obtained in Example 85-1) and 4 M hydrochloric acid (1,4-dioxane solution, 4 mL) in methanol (8 mL) was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, a 5 M aqueous sodium hydroxide solution (40 mL) was added to the residue, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (ethyl acetate:methanol=20:80) to obtain the title compound (460 mg, 88%) as a yellow solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiona 5 M aqueous sodium hydroxide solution (40 mL) was added to the residue
  3. extractionthe mixture was extracted with ethyl acetate
  4. washthe organic layer was washed with saturated sodium chloride solution
  5. dry with materialdried with anhydrous sodium sulfate
  6. concentrationAfter concentration under reduced pressure
  7. customthe residue was purified by silica gel chromatography (ethyl acetate:methanol=20:80)

Sources & evidence

ORD record
ord-0934eb0c56114f55b496b124ef454279
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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