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

HRID 1507208Notes

Reaction equation

HRID 1507208 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 118207501(3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine-1-carboxylate

Product 1

HCID 118207361(3S,4S)-3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine hydrochloride

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a stirring solution of (3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine-1-carboxylate (E-1, the first eluting enantiomer from step F, 44 mg, 0.134 mmol) in 1,4-dioxane (3 mL) at 0° C. was added 2 mL (8 mmol) of 4 M HCl in dioxane, and the resulting mixture was stirred at rt for 12 h. The solvent was removed under reduced pressure to afford (3S,4S)-3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidine hydrochloride (30 mg) as a white solid which was used without further purification. LCMS (Method J) RT=0.60 min, m/z 228.2 (M+H+). 1H NMR (400 MHz, methanol-d4) δ ppm 7.01-7.19 (m, 3H) 4.88-4.99 (m, 1H) 4.71-4.83 (m, 1H) 3.89 (s, 3H) 3.67-3.78 (m, 1H) 3.40-3.53 (m, 1H) 3.00-3.25 (m, 3H) 2.12-2.27 (m, 1H) 1.93-2.08 (m, 1H).

Workup

  1. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-892589a39b7141ae852d93c653e75bf4
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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