Methyl phenyl sulfone → 6-(2-Ethylhexanamido)-1-[2-methoxy-4-[2-(phenylsulphonyl)acetyl]benzyl]indole

HRID 1904456Notes

Reaction equation

HRID 1904456 reaction equation
C([Li])CCC.[C:6]1([S:12]([CH3:15])(=[O:14])=[O:13])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C1(N(C2C=CC=CC=2)C([O:25][C:26](=O)[C:27]2[CH:32]=[CH:31][C:30]([CH2:33][N:34]3[C:42]4[C:37](=[CH:38][CH:39]=[C:40]([NH:43][C:44](=[O:52])[CH:45]([CH2:50][CH3:51])[CH2:46][CH2:47][CH2:48][CH3:49])[CH:41]=4)[CH:36]=[CH:35]3)=[C:29]([O:53][CH3:54])[CH:28]=2)=O)C=CC=CC=1.P([O-])(O)(O)=O.[K+]>O1CCCC1>[CH2:50]([CH:45]([CH2:46][CH2:47][CH2:48][CH3:49])[C:44]([NH:43][C:40]1[CH:41]=[C:42]2[C:37]([CH:36]=[CH:35][N:34]2[CH2:33][C:30]2[CH:31]=[CH:32][C:27]([C:26](=[O:25])[CH2:15][S:12]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)(=[O:14])=[O:13])=[CH:28][C:29]=2[O:53][CH3:54])=[CH:38][CH:39]=1)=[O:52])[CH3:51]

Participants

6

Reactant 4

HCID 18369Methyl phenyl sulfoneHCID 516951Monobasic potassium phosphateHCID 147530114-[6-(2-ethylhexanamido)indole-1-yl-methyl]-3-methoxybenzoic N,N-diphenylcarbamic anhydrideHCID 178418339Butyllithium

Product 1

HCID 147530706-(2-Ethylhexanamido)-1-[2-methoxy-4-[2-(phenylsulphonyl)acetyl]benzyl]indoleYield 44.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of butyllithium (0.86 ml of a 2.3M solution in hexanes) was added to a solution of methyl phenyl sulphone (312 mg) in dry tetrahydrofuran (THF) (5 ml.) at -78° C. After 15 minutes a white suspension formed. To this mixture was then added a solution of 4-[6-(2-ethylhexanamido)indole-1-yl-methyl]-3-methoxybenzoic N,N-diphenylcarbamic anhydride (A) (500 mg) in THF (4 ml). After two hours, the mixture was allowed to warm to ambient temperature and an excess of a saturated solution of potassium dihydrogen phosphate was added. The solvent was removed by evaporation and the residue was partitioned between water and ethyl acetate. The organic phase was dried (Na2SO4) and evaporated. The residual gum was purified by chromatography on silica gel (20 g), using 2:98 v/v ether:methylene chloride as eluent, to give the title compound as a white solid (200 mg, 44%); mp 131°-133° C.

Workup

  1. customAfter 15 minutes a white suspension formed
  2. customThe solvent was removed by evaporation
  3. customthe residue was partitioned between water and ethyl acetate
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated
  6. customThe residual gum was purified by chromatography on silica gel (20 g)

Sources & evidence

ORD record
ord-298b5c9017c04d1ea6b479ebe7d08515
Source dataset
uspto-grants-1989_06
Patent number
US04837235

Reaction notes

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