2-Methylindole → HCID 9947106, compound

HRID 1095601Notes

Reaction equation

HRID 1095601 reaction equation
C[C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.[C:11]([Li])(C)(C)C.CCCCC.[CH2:21]([C:28]1([N:35]([CH3:37])[CH3:36])[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C1COCC1>[CH2:21]([C:28]1([N:35]([CH3:36])[CH3:37])[CH2:29][CH2:30][C:31]([C:2]2[N:3]([CH3:11])[C:4]3[C:9]([CH:10]=2)=[CH:8][CH:7]=[CH:6][CH:5]=3)([OH:34])[CH2:32][CH2:33]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 72242-MethylindoleHCID 8003PentaneHCID 204534784-Benzyl-4-(dimethylamino)cyclohexanoneHCID 178418306HCID 178418306, compound

Product 1

HCID 9947106HCID 9947106, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2-methylindole (500 mg, 3.81 mmol) in dry THF (20 ml) is cooled to −5° C. under a stream of argon. Thereafter, tert-butyllithium (4.19 mmol, 2.47 ml of a 1.7 M pentane solution) is cautiously added dropwise such that a reaction temperature of 0° C. is not thereby exceeded. When the addition has ended, the reaction mixture is stirred at 0° C. for 2 h. Thereafter, a solution of 4-benzyl-4-dimethylaminocyclohexanone (Ket-3, 880 mg, 3.81 mmol) in dry THF (7 ml) is added dropwise at 0° C. The mixture is stirred at 0° C. for 15 min and then at room temperature for 4 h. The reaction mixture is quenched with saturated ammonium chloride solution (20 ml), the organic phase is separated off and the aqueous phase is extracted four times with methylene chloride (20 ml). The combined organic phases are dried over sodium sulfate and thereafter the solvent is removed in vacuo. Purification is carried out by means of flash chromatography (silica gel, cyclohexane/EtOAc 8:2). 456 mg (33%) of the desired cyclohexanol with a melting point of m.p.=105-107° C. are obtained. Only 1 of 2 possible diastereoisomers is formed.

Workup

  1. additionWhen the addition
  2. stirringThe mixture is stirred at 0° C. for 15 min
  3. waitat room temperature for 4 h
  4. customThe reaction mixture is quenched with saturated ammonium chloride solution (20 ml)
  5. customthe organic phase is separated off
  6. extractionthe aqueous phase is extracted four times with methylene chloride (20 ml)
  7. dry with materialThe combined organic phases are dried over sodium sulfate
  8. customthe solvent is removed in vacuo
  9. customPurification

Sources & evidence

ORD record
ord-a86183b2e81446a48c19fe557b7c78e6
Source dataset
uspto-grants-2012_03
Patent number
US08138187B2

Reaction notes

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