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

HRID 1404986Notes

Reaction equation

HRID 1404986 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.[F:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].O>COCCOC.O.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>[F:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[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

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 86668486tert-butyl (2S)-8-bromo-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylate

Product 1

HCID 86668488tert-butyl (2S)-8-(2-fluorophenyl)-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylateYield 98%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

A mixed solution of tert-butyl (2S)-8-bromo-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepine-4(5H)-carboxylate (681 mg) obtained in Example 12, steps 1-4, (2-fluorophenyl)boronic acid (356 mg), dichlorobis(triphenylphosphine)palladium (68 mg) and potassium carbonate (809 mg) in DME-water (1:1, 20 mL) was stirred at 85° C. for 4 hr under a nitrogen stream. The reaction solution was cooled to room temperature, and water was added. The mixture was filtered through celite, and 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→15% ethyl acetate/hexane) to give the title compound (694 mg, 98%) as a colorless oil.

Workup

  1. filtrationThe mixture was filtered through celite
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with water and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (solvent gradient; 5→15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f27b5b06a2584c5ca2be9cdf0e38c5fa
Source dataset
uspto-grants-2014_12
Patent number
US08916549B2

Reaction notes

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