Trifluoroacetic acid → (+/-)-3-amino-5-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-morpholinopiperidin-1-yl)-4-chlorobenzonitrile

HRID 921681ノート

反応式

HRID 921681 の反応式
[Si:1]([O:8][C@H:9]1[C@H:14]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH2:13][CH2:12][N:11]([C:21]2[C:22]([Cl:37])=[C:23]([NH:29]C(=O)OC(C)(C)C)[CH:24]=[C:25]([C:27]#[N:28])[CH:26]=2)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>ClCCl>[NH2:29][C:23]1[CH:24]=[C:25]([CH:26]=[C:21]([N:11]2[CH2:12][CH2:13][C@@H:14]([N:15]3[CH2:16][CH2:17][O:18][CH2:19][CH2:20]3)[C@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3])[CH2:10]2)[C:22]=1[Cl:37])[C:27]#[N:28]

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 86708551(+/-)-tert-butyl (3-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-morpholinopiperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate

生成物 1

HCID 86708550(+/-)-3-amino-5-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-morpholinopiperidin-1-yl)-4-chlorobenzonitrile収率 94%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

(+/−)-tert-butyl (3-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-morpholinopiperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate (138 mg, 0.250 mmol) was treated with TFA (25% in 1,2-dichloroethane, 3 mL, 9.73 mmol) at room temperature for 1 h. The reaction mixture was diluted with dichloromethane and washed with cold saturated sodium bicarbonate/1N aqueous sodium hydroxide (pH 10). The layers were separated and aqueous layer was extracted with dichloromethane two more times. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 5-40% ethyl acetate/hexanes). (+/−)-3-amino-5-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-morpholinopiperidin-1-yl)-4-chlorobenzonitrile (106 mg) was obtained as a yellow/brown solid.

後処理

  1. washwashed with cold saturated sodium bicarbonate/1N aqueous sodium hydroxide (pH 10)
  2. customThe layers were separated
  3. extractionaqueous layer was extracted with dichloromethane two more times
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customthe crude product was purified by flash chromatography on silica gel using
  8. washan automated ISCO system (24 g column, eluting with 5-40% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-79be1dd46d4c42ea9a660da3f0b2a0a9
出典データセット
uspto-grants-2016_03
特許番号
US09273057B2

反応ノート

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