2-Pyridinecarboxaldehyde → {5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-3-chloro-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2-fluorophenyl}(pyridin-2-yl)methanol

HRID 245385

反応式

HRID 245385 の反応式
[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]([Cl: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.[N:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[CH:47]=[O:48]>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]([Cl:34])[C:23]([F:35])=[C:22]([CH:47]([C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][N:41]=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

参加物

5

反応物 3

HCID 142732-PyridinecarboxaldehydeHCID 67359669(2R,6S)-[6-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2-chloro-3-fluorophenyl]-2,6-dimethylmorpholine2 回HCID 178418400CID 53628100

生成物 1

HCID 86717851{5-({[tert-butyl(diphenyl)silyl]oxy}methyl)-3-chloro-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-2-fluorophenyl}(pyridin-2-yl)methanol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a stirred solution of (2R,6S)-[6-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2-chloro-3-fluorophenyl]-2,6-dimethylmorpholine (Intermediate 42, 2.0 g, 3.9 mmol) in anhydrous THF (10 mL), sec-Butyl lithium (1.4 M in cyclohexane, 2.1 eq) was added and the solution was stirred for ½ h at −78° C. Pyridine-2-carbaldehyde (0.74 mL, 7.8 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 over anhydrous sodium sulphate. The solvent was removed under vacuum and the residue was purified over silica gel chromatography column using ethyl acetate-pet. ether gradient to obtain product. Yield: 900 mg, (37%)

後処理

  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 over anhydrous sodium sulphate
  6. customThe solvent was removed under vacuum
  7. customthe residue was purified over silica gel chromatography column
  8. customto obtain product

出典と根拠

ORDレコード
ord-870d5a38576941dba0f40eea2b5409f1
出典データセット
uspto-grants-2014_02
特許番号
US08658641B2

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