Benzaldehyde → {5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2,3-difluorophenyl}(phenyl)methanol

HRID 245361Notes

Reaction equation

HRID 245361 reaction equation
[Si:1]([O:18][CH2:19][C:20]1[C:25]([N:26]2[CH2:31][C@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]2)=[C:24]([F:34])[C:23]([F:35])=[CH:22][CH:21]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])(CC)C.[CH:41](=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>C1COCC1>[Si:1]([O:18][CH2:19][C:20]1[C:25]([N:26]2[CH2:31][C@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]2)=[C:24]([F:34])[C:23]([F:35])=[C:22]([CH:41]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[OH:48])[CH:21]=1)([C:14]([CH3:16])([CH3:17])[CH3:15])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 240BenzaldehydeHCID 67357593(2R,6S)-4-(6-((tert-butyldiphenylsilyloxy)methyl)-2,3-difluorophenyl)-2,6-dimethylmorpholine2×HCID 178418400CID 53628100

Product 1

HCID 86658050{5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2,3-difluorophenyl}(phenyl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of (2R,6S)-4-[6-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2,3-difluorophenyl]-2,6-dimethylmorpholine (Intermediate 3, 1 g, 2.0 mmol) in anhydrous THF (10 mL), s-butyllithium (4.5 ml, 1.4M in cyclohexane, 6.3 mmol) was added and stirred for 2 h at −78° C. Benzaldehyde (685 mg, 0.0064 mmol) in THF (5 mL) was added dropwise and the solution was stirred for additional 1 h. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine and dried (Na2SO4), and solvent was removed. The residue was purified over a silica gel chromatography column using ethyl acetate-pet. ether gradient, providing the title compound.

Workup

  1. stirringthe solution was stirred for additional 1 h
  2. customThe reaction mixture was quenched with saturated ammonium chloride solution
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4), and solvent
  6. customwas removed
  7. customThe residue was purified over a silica gel chromatography column

Sources & evidence

ORD record
ord-6d026d91a86c4a92ab638d73846704b2
Source dataset
uspto-grants-2014_02
Patent number
US08658641B2

Reaction notes

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