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Cyclohexanol → 1h-Indole-1-carboxylic acid,5-[(cyclohexyloxy)methyl]-,1,1-dimethylethyl ester

HRID 252053
Notes
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Reaction equation

HRID 252053 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17]Cl)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:19]1([OH:25])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>C(OCC)C>[C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:17][O:25][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 7966CyclohexanolHCID 66891608tert-Butyl 5-(chloromethyl)-1H-indole-1-carboxylate

Product 1

HCID 231479451h-Indole-1-carboxylic acid,5-[(cyclohexyloxy)methyl]-,1,1-dimethylethyl esterYield 28%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
35 °C

Procedure

A mixture of 5-chloromethyl-indole-1-carboxylic acid tert-butyl ester (0.41 g, 1.55 mmol, 1.0 eq.), cyclohexanol (0.82 mL, 5.0 eq.) and Ag2O (1.80 g, 5.0 eq.) in diethyl ether (5 mL) was stirred at 35° C. over weekend. After cooling to room temperature, the reaction mixture was filtered through celite washing with ether. The filtrate was concentrated and the residue was purified by chromatography (3% EtOAc/hexanes) to give N-Boc-5-cyclohexyloxymethylindole (160 mg, 28%) as colorless oil. 1HNMR confirmed the compound.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe reaction mixture was filtered
  3. washthrough celite washing with ether
  4. concentrationThe filtrate was concentrated
  5. customthe residue was purified by chromatography (3% EtOAc/hexanes)

Sources & evidence

ORD record
ord-c0782adb1e2f4b28b902b049972abf53
Source dataset
uspto-grants-2011_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07868002B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes