Hydrochloric Acid → (3R,4R)-3-Fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine hydrochloride

HRID 1507211Notes

Reaction equation

HRID 1507211 reaction equation
[F:1][C@@H:2]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([F:16])[CH:9]=2)[CH2:6][CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.[ClH:24]>O1CCOCC1>[ClH:24].[F:1][C@@H:2]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([F:16])[CH:9]=2)[CH2:6][CH2:5][NH:4][CH2:3]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 118207594(3R,4R)-tert-butyl 3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine-1-carboxylate

Product 1

HCID 118207344(3R,4R)-3-Fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine hydrochloride

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a stirring solution of (3R,4R)-tert-butyl 3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine-1-carboxylate (38 mg, 0.12 mmol, E-2, the second eluting enantiomer from step F) in 3 mL of 1,4-dioxane at 0° C. was added 2 mL of 4M HCl in 1,4-dioxane (8 mmol) and the mixture was allowed to warm up to rt over 12 h. The solvent was removed under reduced pressure to to obtain (3R,4R)-3-Fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine hydrochloride (30 mg) as a semi-solid which was used without further purification. LCMS (Method K) RT=0.59 min, m/z 228, m/z 419 (M+H+); 1H NMR (400 MHz, methanol-d4) δ ppm 6.99-7.22 (m, 3H) 4.73-4.84 (m, 1H) 3.89 (s, 3H) 3.67-3.78 (m, 2H) 3.41-3.52 (m, 1H) 3.00-3.25 (m, 3H) 2.09-2.26 (m, 1H) 1.88-2.08 (m, 1H).

Workup

  1. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-7fda951445b245a7b621905a6341f15f
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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