Water → methyl 3-[(9-chloro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzoate

HRID 548742Notes

Reaction equation

HRID 548742 reaction equation
[Si]([O:8][CH2:9][CH2:10][N:11]([CH3:23])[C:12](=[O:22])[C:13]1[CH:18]=[CH:17][C:16](F)=[C:15]([Cl:20])[C:14]=1F)(C(C)(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+].[OH:30][C:31]1[CH:32]=[C:33]([CH:38]=[C:39]([O:41][C@H:42]2[CH2:46][CH2:45][O:44][CH2:43]2)[CH:40]=1)[C:34]([O:36][CH3:37])=[O:35].O>C(#N)C.C(OCC)(=O)C>[Cl:20][C:15]1[C:14]2[O:8][CH2:9][CH2:10][N:11]([CH3:23])[C:12](=[O:22])[C:13]=2[CH:18]=[CH:17][C:16]=1[O:30][C:31]1[CH:32]=[C:33]([CH:38]=[C:39]([O:41][C@H:42]2[CH2:46][CH2:45][O:44][CH2:43]2)[CH:40]=1)[C:34]([O:36][CH3:37])=[O:35]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 57663164N-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)-3-chloro-2,4-difluoro-N-methylbenzamideHCID 59127189Methyl 3-hydroxy-5-{[(3S)-oxolan-3-yl]oxy}benzoate

Product 1

HCID 57663187methyl 3-[(9-chloro-4-methyl-5-oxo-2,3,4,5-tetrahydro-1,4-benzoxazepin-8-yl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzoateYield 25.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3-chloro-2,4-difluoro-N-methylbenzamide (647 mg, 1.78 mmol) in acetonitrile (10 mL) was heated with potassium carbonate (492 mg, 3.56 mmol) and methyl 3-hydroxy-5-[(3S)-tetrahydrofuran-3-yloxy]benzoate (424 mg, 1.78 mmol) at 160° C. for 2.5 hours in a microwave reactor. Water (15 mL) and ethyl acetate (20 mL) was added to the reaction mixture, the layers separated and the aqueous phase extracted with ethyl acetate (3×20 mL). The combined organic extract was washed with brine (10 mL) and dried (MgSO4), filtered and evaporated to a residue which was chromatographed on silica, eluting with 40-100% ethyl acetate in isohexane, to give the desired compound as a clear oil (200 mg).

Workup

  1. customthe layers separated
  2. extractionthe aqueous phase extracted with ethyl acetate (3×20 mL)
  3. extractionThe combined organic extract
  4. washwas washed with brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated to a residue which
  8. customwas chromatographed on silica
  9. washeluting with 40-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-b020cfddb4c243f68310ca9838ded1a5
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

Loading…