2-Methylindole → 1-Cyclohexyl-4-(5-fluoro-2-methoxyphenyl)-2-(indol-2-ylmethyl)-4-methylpentan-2-ol

HRID 1070990Notes

Reaction equation

[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.C([Li])CCC.CC(C)([O-])C.[K+].[CH:22]1([CH2:28][C:29](=[O:43])[CH2:30][C:31]([C:34]2[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=2[O:41][CH3:42])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>C1COCC1>[CH:22]1([CH2:28][C:29]([CH2:1][C:2]2[NH:3][C:4]3[C:9]([CH:10]=2)=[CH:8][CH:7]=[CH:6][CH:5]=3)([OH:43])[CH2:30][C:31]([C:34]2[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=2[O:41][CH3:42])([CH3:33])[CH3:32])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1

Participants

Conditions

Temperature: -20 °C

Procedure

To a solution of the 2-methylindole (65 mg) in THF (1 mL) stirred under argon cooled on dry ice/acetone was added n-butyl lithium (2 M in pentane, 0.8 mL). After 2 minutes, potassium tert-butoxide (1M in THF, 1 mL) was added and the mixture was allowed to warm to approximately −20° C. After 5 minutes, a precipitate was noted and the mixture was cooled to −70° C. 1-Cyclohexyl-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one (Example 15) (100 mg) in THF (1 mL) was added dropwise and the mixture was stirred for 20 minutes at −70° C. The reaction was quenched with EtOH (0.5 mL). The mixture was diluted with EtOAc, washed with water, dried, filtered, and evaporated. Chromatography over silica gel (methylene chloride-hexanes (1:2)) gave the title compound as an oil (0.095 g).

Workup

temperaturecooled on dry ice/acetone
waitAfter 5 minutes
temperaturethe mixture was cooled to −70° C
customThe reaction was quenched with EtOH (0.5 mL)
additionThe mixture was diluted with EtOAc
washwashed with water
customdried
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-53f2cb0816f04fd29619eb7b16e0c273
Source dataset: uspto-grants-2005_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06903215B2

Reaction notes

Loading…