Oxazole → (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

HRID 1424132Notes

Reaction equation

HRID 1424132 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:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])([CH3:21])[CH2:20][C:14]4=[N:13][N:12]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[O:31]1[CH:35]=[CH:34][N:33]=[CH:32]1.CC(C)([O-])C.[Li+].[Cl-].[NH4+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Si:24]([O:23][CH2:22][C@:19]1([CH3:21])[S:18][CH2:17][CH2:16][N:15]2[C:11]([C:8]3([C:5]4[CH:6]=[CH:7][C:2]([C:32]5[O:31][CH:35]=[CH:34][N:33]=5)=[CH:3][CH:4]=4)[CH2:10][CH2:9]3)=[N:12][N:13]=[C:14]2[CH2:20]1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]

Participants

7

Reactant 4

HCID 9255OxazoleHCID 25517Ammonium ChlorideHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 86712920(8R)-3-[1-(4-Bromophenyl)cyclopropyl]-8-({[t-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 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]thiazepineYield 86.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of the compound (800 mg, 1.57 mmol) obtained in Example 52-1), oxazole (217 mg, 3.15 mmol), tetrakis(triphenylphosphine)palladium(0) (91 mg, 0.08 mmol), and lithium tert-butoxide (260 mg, 3.15 mmol) in dioxane (12 mL) was stirred for 2 h with heating to reflux. The reaction mixture was cooled to room temperature, saturated aqueous ammonium chloride (50 mL) was added to the reaction mixture, 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=70:30) to obtain the title compound (674 mg, 86%) in a yellow oily form.

Workup

  1. temperaturewith heating to reflux
  2. extractionthe mixture was extracted with ethyl acetate
  3. washthe organic layer was washed with saturated sodium chloride solution
  4. dry with materialdried with anhydrous sodium sulfate
  5. concentrationAfter concentration under reduced pressure
  6. customthe residue was purified by silica gel chromatography (ethyl acetate:methanol=70:30)

Sources & evidence

ORD record
ord-90690672e5da4d89ae53f24552eeb808
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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