Lithium naphthalenide → (1R,2R,5R*)-8-Benzyl-1-(4-fluorophenyl)-8-azabicyclo[3.2.1]octan-2-ol

HRID 2088101Notes

Reaction equation

[CH2:1]([N:8]1[C@@H:13]2[C@H:14](S(C3C=CC=CC=3)(=O)=O)[CH2:15][C@@:9]1([C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)[C@H:10]([OH:25])[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C-]1C2C(=CC=CC=2)C=CC=1.[Li+]>C1COCC1>[CH2:1]([N:8]1[C@@H:13]2[CH2:14][CH2:15][C@@:9]1([C:26]1[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=1)[C@H:10]([OH:25])[CH2:11][CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -78 °C

Procedure

(1R*,2R*,5S*,6R*)-8-Benzyl-1-(4-fluorophenyl)-6-phenylsulphonyl-8-azabicyclo[3.2.1]octan-2-ol (Description 14; 10.72 g, 23.77 mmol) was dissolved in THF (200 ml) then cooled to −78° C. and lithium naphthalenide added until a permanent green colour was observed. Each portion was then quenched with saturated ammonium chloride solution then extracted with ethyl acetate (×3) and the extracts dried (MgSO4) and concentrated in vacuo. The extracts were combined to give a yellow oil/solid. This was purified by flash column chromatography [20%-40% ethyl acetate in iso-hexane] to give a yellow solid which was repurified by flash column chromatography [25% ethyl acetate in iso-hexane] to give the title compound as a clear yellow oil (5.37 g, 73%).

Workup

customEach portion was then quenched with saturated ammonium chloride solution
extractionthen extracted with ethyl acetate (×3)
dry with materialthe extracts dried (MgSO4)
concentrationconcentrated in vacuo
customto give a yellow oil/solid
customThis was purified by flash column chromatography [20%-40% ethyl acetate in iso-hexane]
customto give a yellow solid which
customwas repurified by flash column chromatography [25% ethyl acetate in iso-hexane]

Sources & evidence

ORD record: ord-6702ffd841f74f718ba8995f3f3c4d33
Source dataset: uspto-grants-2004_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06727249B2

Reaction notes

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