Water → 2,2-dimethyl-3-[2'-oxo-5'-(pyrrolidin-1-ylsulfonyl)spiro[1,3-dioxane-2,3'-indol]-1'(2'H)-yl]propanenitrile

HRID 853875Notes

Reaction equation

HRID 853875 reaction equation
CC(C)([O-])C.[K+].[N:7]1([S:12]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[NH:20][C:19](=[O:24])[C:18]23[O:29][CH2:28][CH2:27][CH2:26][O:25]2)(=[O:14])=[O:13])[CH2:11][CH2:10][CH2:9][CH2:8]1.Cl[CH2:31][C:32]([CH3:36])([CH3:35])[C:33]#[N:34].O>CS(C)=O>[CH3:31][C:32]([CH3:36])([CH2:35][N:20]1[C:21]2[C:17](=[CH:16][C:15]([S:12]([N:7]3[CH2:11][CH2:10][CH2:9][CH2:8]3)(=[O:13])=[O:14])=[CH:23][CH:22]=2)[C:18]2([O:29][CH2:28][CH2:27][CH2:26][O:25]2)[C:19]1=[O:24])[C:33]#[N:34]

Participants

6

Reactant 4

HCID 962WaterHCID 147139153-Chloro-2,2-dimethylpropanenitrileHCID 23665647Potassium tert-butoxideHCID 589325715'-(pyrrolidin-1-ylsulfonyl)spiro[1,3-dioxane-2,3'-indol]-2'(1'H)-one

Product 1

HCID 589325752,2-dimethyl-3-[2'-oxo-5'-(pyrrolidin-1-ylsulfonyl)spiro[1,3-dioxane-2,3'-indol]-1'(2'H)-yl]propanenitrileYield 77%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

At room temperature, to a stirred solution of potassium t-butoxide (0.287 g, 2.56 mmol, 1.2 eq) in anhydrous DMSO (4 mL) was added 5′-(pyrrolidin-1-ylsulfonyl)spiro[1,3-dioxane-2,3′-indol]-2′(1′H)-one (0.72 g, 2.13 mmol). After stirring 20 minutes, 3-chloro-2,2-dimethylpropionitrile (3 eq) was added drop-wise and the reaction was heated at 130° C. for 20 hr. The reaction mixture was heated at 126° C. for 16 h. After cooling to room temperature, the reaction was poured into H2O (100 mL) and extracted with Et2O (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated. The crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH H4OH (97/2/1) followed by a second chromatography eluting with 50/50 Pet. ether/EtOAc to give the title compound as a white solid (0.69 g, 77% yield). NMR: consistent.

Workup

  1. temperatureThe reaction mixture was heated at 126° C. for 16 h
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with Et2O (3×)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified on Biotage KP silica gel eluting with CH2Cl2/CH3OH H4OH (97/2/1)
  8. washeluting with 50/50 Pet. ether/EtOAc

Sources & evidence

ORD record
ord-15883286c48a40f69b8e82f062f608fd
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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