Boron trifluoride etherate → (3R)-3-(3-cyclohexyl-3-phenyl-1-propynyl)-1-azabicyclo[2.2.2]oct-3-yl methyl ether

HRID 900780Notes

Reaction equation

[CH:1]1([C:7]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(O)[C:8]#[C:9][C@:10]2([O:18][CH3:19])[CH:15]3[CH2:16][CH2:17][N:12]([CH2:13][CH2:14]3)[CH2:11]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[SiH](CC)(CC)CC.B(F)(F)F.CCOCC>C(Cl)Cl>[CH3:19][O:18][C@@:10]1([C:9]#[C:8][CH:7]([CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:15]2[CH2:16][CH2:17][N:12]([CH2:13][CH2:14]2)[CH2:11]1

Participants

Conditions

Temperature: -40 °C

Procedure

1-cyclohexyl-3-[(3R)-3-methoxy-1-azabicyclo[2.2.2]oct-3-yl]-1-phenyl-2-propyn-1-ol 201 (150 mg, 0.42 mmol) was dissolved under argon in CH2Cl2 (20 ml) and then cooled to −40° C. Neat Et3SiH (203 μL, 1.27 mmol) was added dropwise. After 5 minutes, neat BF3.OEt2 (376 μL, 1.27 mmol) was slowly added to the mixture. After 15 minutes, the reaction was slowly left to room temperature, then quenched with saturated aqueous K2CO3 solution after 45 minutes and diluted with ether. The organic phase was dried over Na2SO4 and evaporated to dryness to give (3R)-3-(3-cyclohexyl-3-phenyl-1-propynyl)-1-azabicyclo[2.2.2]oct-3-yl methyl ether 112 (mixture of diastereomers) as a colorless oil (140 mg, 97%).

Workup

waitAfter 15 minutes
waitthe reaction was slowly left to room temperature
customquenched with saturated aqueous K2CO3 solution after 45 minutes
additiondiluted with ether
dry with materialThe organic phase was dried over Na2SO4
customevaporated to dryness

Sources & evidence

ORD record: ord-0b1e9707afbd4f38ac9c6a2f3da37b6d
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07361668B2

Reaction notes

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