Dimethyl Sulfoxide → 3-[5'-({(2S)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}sulfonyl)-2'-oxospiro[1,3-dioxane-2,3'-indol]-1'(2'H)-yl]-2,2-dimethylpropanenitrile

HRID 853863ノート

反応式

HRID 853863 の反応式
CC(C)([O-])C.[K+].CS(C)=O.[CH2:11]([O:18][CH2:19][C@@H:20]1[CH2:24][CH2:23][CH2:22][N:21]1[S:25]([C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][C:32](=[O:37])[C:31]12[O:42][CH2:41][CH2:40][CH2:39][O:38]1)(=[O:27])=[O:26])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl[CH2:44][C:45]([CH3:49])([CH3:48])[C:46]#[N:47]>O>[CH2:11]([O:18][CH2:19][C@@H:20]1[CH2:24][CH2:23][CH2:22][N:21]1[S:25]([C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[N:33]([CH2:44][C:45]([CH3:49])([CH3:48])[C:46]#[N:47])[C:32](=[O:37])[C:31]12[O:38][CH2:39][CH2:40][CH2:41][O:42]1)(=[O:26])=[O:27])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

参加物

6

反応物 4

HCID 679Dimethyl SulfoxideHCID 147139153-Chloro-2,2-dimethylpropanenitrileHCID 23665647Potassium tert-butoxideHCID 589325835'-({(2S)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}sulfonyl)spiro[1,3-dioxane-2,3'-indol]-2'(1'H)-one

生成物 1

HCID 589325233-[5'-({(2S)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}sulfonyl)-2'-oxospiro[1,3-dioxane-2,3'-indol]-1'(2'H)-yl]-2,2-dimethylpropanenitrile収率 66%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
132 °C

実験手順

To a solution of potassium t-butoxide (3.58 g, 31.9 mmol, 1.2 eq) in anhyd DMSO (72 mL) was added 5′-({(2S)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}sulfonyl)spiro[1,3-dioxane-2,3′-indol]-2′(1′H)-one (12.20 g, 26.6 mmol ) all at one time under a dry N2 atmosphere. After stirring 20 minutes, 3-chloro-2,2-dimethylpropionitrile (9.38 g, 79.8 mmol, 3 eq) was added drop-wise and the reaction was heated at 132° C. for 21 hr. After cooling in an ice bath, the reaction mixture was poured into H2O and extracted with Et2O. The combined organic extracts were dried over Na2SO4, filtered and concentrated. The crude product was purified on Biotage KP silica gel using a step gradient of CH2Cl2/CH3OH/NH4OH (99.25/0.5/0.25 to 96/2/1) to give the title compound as a yellow solid (9.48 g, 66% yield). NMR (400 MHz, DMSO-d6): consistent.

後処理

  1. temperatureAfter cooling in an ice bath
  2. extractionextracted with Et2O
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified on Biotage KP silica gel using a step gradient of CH2Cl2/CH3OH/NH4OH (99.25/0.5/0.25 to 96/2/1)

出典と根拠

ORDレコード
ord-aa641ac2d1cf4d0b8ee1e63e552263a0
出典データセット
uspto-grants-2007_08
特許番号
US07256198B2

反応ノート

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