Water → tert-butyl (2S)-2-methyl-8-(1-methylethyl)-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylate

HRID 1404988Notes

Reaction equation

HRID 1404988 reaction equation
Br[C:2]1[C:11]2[O:10][C@@H:9]([CH3:12])[CH2:8][N:7]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:6][C:5]=2[S:4][CH:3]=1.[C:20](B1OC(C)(C)C(C)(C)O1)([CH3:22])=[CH2:21].C(=O)([O-])[O-].[K+].[K+].O>COCCOC.O.C1COCC1.CO.[Pd].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:12][C@H:9]1[CH2:8][N:7]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:6][C:5]2[S:4][CH:3]=[C:2]([CH:20]([CH3:22])[CH3:21])[C:11]=2[O:10]1

Participants

9

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 86668486tert-butyl (2S)-8-bromo-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylate

Product 1

HCID 86668493tert-butyl (2S)-2-methyl-8-(1-methylethyl)-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylateYield 90%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A mixed solution of tert-butyl (2S)-8-bromo-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylate (1.15 g) obtained in Example 12, steps 1-4, isopropenylboronic acid pinacol ester (0.807 mL), dichlorobis(triphenylphosphine)palladium (116 mg) and potassium carbonate (1.37 g) in DME-water (1:1, 30 mL) was stirred at 85° C. for 2 hr under a nitrogen stream. The reaction solution was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient; 5→12% ethyl acetate/hexane) to give a colorless oil. To a solution of the obtained oil in THF-MeOH (2:1, 30 mL) was added 10% palladium on carbon (100 mg), and the mixture was stirred for 1 hr under a hydrogen atmosphere. The reaction solution was filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient; 0→10% ethyl acetate/hexane) to give the title compound (926 mg, 90%) as a colorless oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (solvent gradient; 5→12% ethyl acetate/hexane)
  6. customto give a colorless oil
  7. filtrationThe reaction solution was filtered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (solvent gradient; 0→10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-7812b41c37af44aebe5f2a6cf09fe396
Source dataset
uspto-grants-2014_12
Patent number
US08916549B2

Reaction notes

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