Dimethyl Sulfoxide → 1,1-Dimethylethyl 4-(3-{6-[(2,2-dimethylpropanoyl)amino]-2-fluoro-3-pyridinyl}-3-oxopropyl)-1-piperidinecarboxylate

HRID 489790ノート

反応式

HRID 489790 の反応式
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][C:12]([CH3:41])([CH3:40])[C:13]([NH:15][C:16]1[N:21]=[C:20]([F:22])[C:19]([CH:23]([OH:39])[CH2:24][CH2:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)=[CH:18][CH:17]=1)=[O:14].C(N(CC)CC)C>ClCCl>[CH3:11][C:12]([CH3:41])([CH3:40])[C:13]([NH:15][C:16]1[N:21]=[C:20]([F:22])[C:19]([C:23](=[O:39])[CH2:24][CH2:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]2)=[CH:18][CH:17]=1)=[O:14]

参加物

6

反応物 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 222626141,1-Dimethylethyl 4-(3-{6-[(2,2-dimethylpropanoyl)amino]-2-fluoro-3-pyridinyl}-3-hydroxypropyl)-1-piperidinecarboxylate

生成物 1

HCID 222626761,1-Dimethylethyl 4-(3-{6-[(2,2-dimethylpropanoyl)amino]-2-fluoro-3-pyridinyl}-3-oxopropyl)-1-piperidinecarboxylate収率 73%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of oxalyl chloride (0.11 ml, 1.25 mmol) in dichloromethane (10 ml) was added dropwise dimethylsulfoxide (0.18 ml, 2.51 mmol) at −78° C. After stirring for 10 min, a solution of 1,1-dimethylethyl 4-(3-{6-[(2,2-dimethylpropanoyl)amino]-2-fluoro-3-pyridinyl}-3-hydroxypropyl)-1-piperidinecarboxylate (step 1, 500 mg, 1.14 mmol) in dichloromethane (5 ml) was added to the mixture at −78° C. After 15 min, triethylamine (0.79 ml, 5.70 mmol) was added at the same temperature and the resulting mixture was allowed to warm up to room temperature and stirred for 18 h. The mixture was quenched with 1N aqueous hydrochloric acid (100 ml) and extracted with dichloromethane (150 ml). The organic layer was washed with water (50 ml) and dried over magnesium sulfate. Removal of solvent gave a pale yellow solid, which was chromatographed on a column of silica gel eluting with ethyl acetate/hexane (4:1 ) to afford 362 mg (73%) of the title compound as a white solid.

後処理

  1. waitAfter 15 min
  2. stirringstirred for 18 h
  3. customThe mixture was quenched with 1N aqueous hydrochloric acid (100 ml)
  4. extractionextracted with dichloromethane (150 ml)
  5. washThe organic layer was washed with water (50 ml)
  6. dry with materialdried over magnesium sulfate
  7. customRemoval of solvent
  8. customgave a pale yellow solid, which
  9. customwas chromatographed on a column of silica gel eluting with ethyl acetate/hexane (4:1 )

出典と根拠

ORDレコード
ord-f08ad051933f4437a77e641b3bed07b2
出典データセット
uspto-grants-2005_12
特許番号
US06979690B2

反応ノート

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