Triphenylphosphine → 2-[(4-{[Tert-butyl(dimethyl)silyl]oxy}phenoxy)methyl]-5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydro[1,3]oxazolo[5,4-c]pyridine

HRID 1529572Notes

Reaction equation

HRID 1529572 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[F:17][C:18]1[CH:37]=[CH:36][C:21]([C:22]([N:24]2[CH2:30]C[C:28]3[O:31][C:32]([CH2:34][OH:35])=[N:33][C:27]=3[CH2:26][CH2:25]2)=[O:23])=[CH:20][CH:19]=1.[C:38]([Si:42]([CH3:52])([CH3:51])[O:43][C:44]1[CH:49]=[CH:48][C:47](O)=[CH:46][CH:45]=1)([CH3:41])([CH3:40])[CH3:39].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.[OH-].[Na+]>[Si:42]([O:43][C:44]1[CH:45]=[CH:46][C:47]([O:35][CH2:34][C:32]2[O:31][C:28]3[CH2:30][N:24]([C:22]([C:21]4[CH:20]=[CH:19][C:18]([F:17])=[CH:37][CH:36]=4)=[O:23])[CH2:25][CH2:26][C:27]=3[N:33]=2)=[CH:48][CH:49]=1)([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:52])[CH3:51]

Participants

7

Reactant 4

HCID 11776Triphenylphosphine2×HCID 97268Di-tert-butyl azodicarboxylate2×HCID 5973884-(tert-Butyldimethylsiloxy)phenol2×HCID 666088636-(4-fluorobenzoyl)-5,6,7,8-tetrahydro-4H-oxazolo[4,5-d]azepine-2-methanol

Product 1

HCID 666088752-[(4-{[Tert-butyl(dimethyl)silyl]oxy}phenoxy)methyl]-5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydro[1,3]oxazolo[5,4-c]pyridineYield 151.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

Di-tert-butyl azodicarboxylate (0.1 g, 0.43 mmol) was added to a stirred solution of 6-(4-fluorobenzoyl)-5,6,7,8-tetrahydro-4H-oxazolo[4,5-d]azepine-2-methanol (0.1 g, 0.36 mmol), 4-(tert-butyl-dimethyl-silanyloxy)-phenol (0.097 g, 0.43 mmol) and triphenylphosphine (0.114 g, 0.43 mmol) in THF (0.5 mL) at 0° C. The mixture was stirred at room temperature for 16 hours. Additional di-tert-butyl azodicarboxylate (0.1 g, 0.43 mmol), 4-(tert-butyl-dimethyl-silanyloxy)-phenol (0.097 g, 0.43 mmol) and triphenylphosphine (0.114 g, 0.43 mmol) were added at 0° C. The mixture was stirred at 120° C. for 20 minutes under microwave irradiation. The mixture was diluted with a 1M aqueous solution of NaOH and washed with AcOEt. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 30/70). The desired fractions were collected and the solvents evaporated in vacuo to yield 2-[(4-{[tert-butyl(dimethyl)silyl]oxy}phenoxy)methyl]-5-[(4-fluorophenyl)carbonyl]-4,5,6,7-tetrahydro[1,3]oxazolo[5,4-c]pyridine (264 mg, 66% purity, 99% yield) as a colorless oil. C26H31FN2O4Si.

Workup

  1. stirringThe mixture was stirred at 120° C. for 20 minutes under microwave irradiation
  2. washwashed with AcOEt
  3. customThe organic layer was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvents evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 0/100 to 30/70)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-b2f750c80a9d443a9e8cf3c34bf54a1b
Source dataset
uspto-grants-2015_07
Patent number
US09090632B2

Reaction notes

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