3-Chloro-2-chloromethyl-1-propene → HCID 66674413, compound

HRID 421934Notes

Reaction equation

HRID 421934 reaction equation
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[NH:9][C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[OH:26])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:27][C:28]([O-])([CH3:30])[CH3:29].[K+].ClCC(CCl)=C>CN(C=O)C>[CH:1]1([C:7]2[C:15]3[CH:14]=[CH:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:10]=3[N:9]3[C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[O:26][CH2:30][C:28](=[CH2:27])[CH2:29]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 158593-Chloro-2-chloromethyl-1-propeneHCID 11995228Methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 66674413HCID 66674413, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylate (prepared as described in International patent application publication WO2006/046030, Example 9)(0.12 M) in DMF was treated with KOtBu (2.1 eq.) in one portion; the resulting mixture was stirred for 30 min at RT then treated dropwise with 3-chloro-2-(chloromethyl)prop-1-ene (1.1 eq.). The resulting solution was stirred at RT overnight before being quenched by addition of HCl (1N) and extracted into EtOAc. The combined organic layers were washed with sat. aq. NaHCO3 and brine, before being dried (Na2SO4), filtered and concentrated in vacuo. The crude material was purified by FC (PE/EtOAc 85:15) affording the product as a yellow oil (97%). (ES+) m/z 402 (M+H)+.

Workup

  1. stirringThe resulting solution was stirred at RT overnight
  2. custombefore being quenched by addition of HCl (1N)
  3. extractionextracted into EtOAc
  4. washThe combined organic layers were washed with sat. aq. NaHCO3 and brine
  5. dry with materialbefore being dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by FC (PE/EtOAc 85:15)

Sources & evidence

ORD record
ord-f8eda9e47a2f48dfba179bdccb8f7bae
Source dataset
uspto-grants-2012_01
Patent number
US08101595B2

Reaction notes

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