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 853863Notes

Reaction equation

HRID 853863 reaction equation
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

Participants

6

Reactant 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

Product 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-dimethylpropanenitrileYield 66%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
132 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-aa641ac2d1cf4d0b8ee1e63e552263a0
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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