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

HRID 1404987Notes

Reaction equation

HRID 1404987 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.[CH:20]1(B(O)O)[CH2:22][CH2:21]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.CC(C)([O-])C.[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH:20]1([C:2]2[C:11]3[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]=3[S:4][CH:3]=2)[CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 23665647Potassium tert-butoxideHCID 86668486tert-butyl (2S)-8-bromo-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylate

Product 1

HCID 86668489tert-butyl (2S)-8-cyclopropyl-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylateYield 83%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of tert-butyl (2S)-8-bromo-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylate (616 mg) obtained in Example 12, steps 1-4, cyclopropylboronic acid (228 mg), palladium acetate (20 mg), tricyclohexylphosphine (50 mg), potassium tert-butoxide (595 mg) and toluene (20 ml) was stirred at 80° C. for 14 hr under an argon atmosphere. The reaction solution was cooled to room temperature, and filtered through celite. 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; 0→10% ethyl acetate/hexane) to give the title compound (453 mg, 83%) as a colorless oil.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. filtrationfiltered through celite
  3. additionWater was added
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with water and saturated brine
  6. dry with materialdried over magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (solvent gradient; 0→10% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-41cf08c23a7d493d972fff3e58bf19a9
Source dataset
uspto-grants-2014_12
Patent number
US08916549B2

Reaction notes

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