Potassium Carbonate → methyl 2-(5,5-dimethyl-5'-(N-(2-morpholinoethyl)-methylsulfonamido)-2'-oxospiro[[1,3]dioxane-2,3'-indoline]-1'-yl)acetate

HRID 571325Notes

Reaction equation

HRID 571325 reaction equation
[CH3:1][C:2]1([CH3:27])[CH2:26][O:25][C:5]2([C:13]3[C:8](=[CH:9][CH:10]=[C:11]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:12]=3)[N:7]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:6]2=[O:24])[O:4][CH2:3]1.Cl.Cl[CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:1][C:2]1([CH3:27])[CH2:3][O:4][C:5]2([C:13]3[C:8](=[CH:9][CH:10]=[C:11]([N:14]([CH2:30][CH2:31][N:32]4[CH2:37][CH2:36][O:35][CH2:34][CH2:33]4)[S:15]([CH3:18])(=[O:17])=[O:16])[CH:12]=3)[N:7]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:6]2=[O:24])[O:25][CH2:26]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 86681649Methyl 2-(5,5-dimethyl-5'-(methylsulfonamido)-2'-oxospiro[[1,3]dioxane-2,3'-indoline]-1'-yl)acetate

Product 1

HCID 86681740methyl 2-(5,5-dimethyl-5'-(N-(2-morpholinoethyl)-methylsulfonamido)-2'-oxospiro[[1,3]dioxane-2,3'-indoline]-1'-yl)acetateYield 88.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of methyl 2-(5,5-dimethyl-5′-(methylsulfonamido)-2′-oxospiro[[1,3]dioxane-2,3′-indoline]-1′-yl)acetate (0.400 g, 1.004 mmol), 4-(2-chloroethyl)morpholine hydrochloride (0.224 g, 1.204 mmol) (prepared in an analogous manner as described in Example 17, Scheme 17, Steps 1, 2, 3, 4) and K2CO3 (0.306 g, 2.208 mmol) in DMF (8 ml) was heated at 70° C. for 3 hours. The mixture was partitioned between ethyl acetate and water, and the aqueous phase was extracted with ethyl acetate. The combined organic layers were washed several times with brine and dried over sodium sulfate; the solvent was removed and the crude was purified by chromatography on silica gel cartridge (DCM:MeOH=99:1 to 97:3) affording methyl 2-(5,5-dimethyl-5′-(N-(2-morpholinoethyl)-methylsulfonamido)-2′-oxospiro[[1,3]dioxane-2,3′-indoline]-1′-yl)acetate (0.453 g, 0.885 mmol, 88% yield, MS/ESI+ 512.1 [MH]+).

Workup

  1. customprepared in an analogous manner
  2. customThe mixture was partitioned between ethyl acetate and water
  3. extractionthe aqueous phase was extracted with ethyl acetate
  4. washThe combined organic layers were washed several times with brine
  5. dry with materialdried over sodium sulfate
  6. customthe solvent was removed
  7. customthe crude was purified by chromatography on silica gel cartridge (DCM:MeOH=99:1 to 97:3)

Sources & evidence

ORD record
ord-a332736939044158985a23ed82597019
Source dataset
uspto-grants-2015_05
Patent number
US09024027B2

Reaction notes

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