Hydrochloric Acid → Methyl 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoate

HRID 327220Notes

Reaction equation

HRID 327220 reaction equation
[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([OH:16])=[CH:13][CH:14]=3)[C:9]([S:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[C:8]2[CH2:22][C:23]([CH3:29])([CH3:28])[C:24]([O:26][CH3:27])=[O:25])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].C([O-])([O-])=O.[Cs+].[Cs+].Cl.Cl[CH2:46][C:47]1[CH:56]=[CH:55][C:54]2[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=2)[N:48]=1.Cl>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16][CH2:46][C:47]4[CH:56]=[CH:55][C:54]5[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=5)[N:48]=4)=[CH:13][CH:14]=3)[C:9]([S:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[C:8]2[CH2:22][C:23]([CH3:29])([CH3:28])[C:24]([O:26][CH3:27])=[O:25])=[CH:30][CH:31]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 30838232-(Chloromethyl)quinoline hydrochlorideHCID 14980577Methyl 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-hydroxy-1H-indol-2-yl)-2,2-dimethylpropanoate

Product 1

HCID 15225389Methyl 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Methyl 3-[N-(p-chlorobenzyl)-5-hydroxy-3-(t-butylthio)indol-2-yl]-2,2-dimethylpropanoate (33.6 g) from Step C was dissolved in 500 mL of dry DMF and the solution was charged with 2.4 g of KI, 30.3 g of K2CO3, 4.77 g of Cs2CO3 and 23.5 g of 2-(chloromethyl)quinoline hydrochloride. The reaction was stirred at RT, under N2, for 72 hours then it was poured into water (1.5 L), acidified with 1N HCl and extracted (3×200 mL) with CH2Cl2. The organic phase was washed with H2O (3×150 mL), dried and evaporated. The residue was dissolved in hot EtOAc and upon cooling crystallized to deposit 22.0 g of the title compound, m.p. 166°-167° C.

Workup

  1. extractionextracted (3×200 mL) with CH2Cl2
  2. washThe organic phase was washed with H2O (3×150 mL)
  3. customdried
  4. customevaporated
  5. dissolutionThe residue was dissolved in hot EtOAc
  6. temperatureupon cooling
  7. customcrystallized

Sources & evidence

ORD record
ord-462d1aff2f2c4108820bd23d9b1ff74f
Source dataset
uspto-grants-1993_12
Patent number
US05272145

Reaction notes

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