Potassium Hydroxide → methyl 1-cyclohexylmethyl-3-methyl-1H-indole-6-carboxylate

HRID 2054502Notes

Reaction equation

HRID 2054502 reaction equation
[CH3:1][C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:9]=2)[NH:4][CH:3]=1.[CH:15]1([CH2:21]Br)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.[OH-].[K+]>CC(C)=O.[I-].[Na+]>[CH:15]1([CH2:21][N:4]2[C:5]3[C:10](=[CH:9][CH:8]=[C:7]([C:11]([O:13][CH3:14])=[O:12])[CH:6]=3)[C:2]([CH3:1])=[CH:3]2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 137636Cyclohexane, (bromomethyl)-HCID 21938240Methyl 3-methyl-1H-indole-6-carboxylate

Product 1

HCID 22663183methyl 1-cyclohexylmethyl-3-methyl-1H-indole-6-carboxylateYield 63%

Reagents, catalysts & solvents 2

HCID 5238Sodium IodideCatalystHCID 180AcetoneSolvent

Procedure

A mixture of methyl 3-methyl-1H-indole-6-carboxylate(10 g, Reference Example 30), cyclohexylmethylbromide (19 g), potassium hydroxide (12 g) and sodium iodide (0.1 g) in acetone (200 ml) was stirred at room temperature for 6 hours. The reaction mixture was evaporated. The residue was partitioned between ethyl acetate (250 ml) and water (250 ml). The aqueous layer was extracted three times with ethyl acetate (250 ml). The total combined organic phases were dried over sodium sulphate then evaporated. The residue was subjected to flash column chromatography on silica eluting with a mixture of ethyl acetate and hexane (gradient elution, 0:10 to 1:9, v/v)to yield the title compound (9.5 g). NMR (CDCl3): δ 0.90-1.10(m), 1.10-1.40(m), 1.60-1.90(m), 2.30(s), 3.90-4.00(m), 3.90(s), 7.00(s), 7.50-7.60(m), 7.70-7.80(m), 8.00(s). MH+ 271.

Workup

  1. customThe reaction mixture was evaporated
  2. customThe residue was partitioned between ethyl acetate (250 ml) and water (250 ml)
  3. extractionThe aqueous layer was extracted three times with ethyl acetate (250 ml)
  4. dry with materialwere dried over sodium sulphate
  5. customthen evaporated
  6. additionThe residue was subjected to flash column chromatography on silica eluting with a mixture of ethyl acetate and hexane (
  7. washgradient elution, 0:10 to 1:9, v/v)to

Sources & evidence

ORD record
ord-705afdaf5f464e97bae98f49f5916980
Source dataset
uspto-grants-2008_02
Patent number
US07329675B2

Reaction notes

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