Water → (+/-)-cis-({3-[(6-Phenylfuro[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}oxy)acetic acid tert-butyl ester

HRID 2189037ノート

反応式

HRID 2189037 の反応式
[C:1]1([C:7]2[O:23][C:10]3[N:11]=[CH:12][N:13]=[C:14]([NH:15][C@@H:16]4[CH2:21][CH2:20][CH2:19][C@H:18]([OH:22])[CH2:17]4)[C:9]=3[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].[C:26]([O:30][C:31](=[O:34])[CH2:32]Br)([CH3:29])([CH3:28])[CH3:27].O>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.C1COCC1>[C:26]([O:30][C:31](=[O:34])[CH2:32][O:22][C@H:18]1[CH2:19][CH2:20][CH2:21][C@@H:16]([NH:15][C:14]2[C:9]3[CH:8]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[O:23][C:10]=3[N:11]=[CH:12][N:13]=2)[CH2:17]1)([CH3:29])([CH3:28])[CH3:27]

参加物

8

反応物 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 79177tert-Butyl bromoacetateHCID 86653748(+/-)-cis-3-[(6-Phenylfuro[2,3-d]pyrimidin-4-yl)amino]cyclohexanol

生成物 1

HCID 86653749(+/-)-cis-({3-[(6-Phenylfuro[2,3-d]pyrimidin-4-yl)amino]cyclohexyl}oxy)acetic acid tert-butyl ester

試薬・触媒・溶媒 3

HCID 94433Tetrabutylammonium hydrogen sulfate触媒HCID 1140Toluene溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
70 °C

実験手順

At 40° C., add approx. 0.06 mmol of tetrabutylammonium hydrogensulphate and a solution of 200 mg (0.646 mmol) of (+/−)-cis-3-[(6-phenylfuro[2,3-d]pyrimidin-4-yl)amino]cyclohexanol in 0.5 ml of toluene and 0.1 ml of THF to a mixture of 517 mg of 50% sodium hydroxide solution (6.5 mmol) and 0.5 ml of toluene. Admix the resulting mixture with 0.19 ml (1.29 mmol) of bromoacetic acid tert-butyl ester with vigorous stirring and heat it to 70° C. After 2 h, cool the mixture and add it to water. Extract three times with dichloromethane, wash the combined organic phases with saturated sodium chloride solution and concentrate under reduced pressure. After preparative RP-HPLC (eluent: acetonitrile/water), 152 mg (55.5% of theory) of the target product are isolated from the crude product.

後処理

  1. temperaturecool the mixture
  2. extractionExtract three times with dichloromethane
  3. washwash the combined organic phases with saturated sodium chloride solution
  4. concentrationconcentrate under reduced pressure

出典と根拠

ORDレコード
ord-b14def8bf2cc47f3aa2c0a7633a384bc
出典データセット
uspto-grants-2012_12
特許番号
US08324222B2

反応ノート

読み込み中…