Hydrochloric Acid → 2-fluoro-4-((3S,4S)-3-fluoropiperidin-4-yl)phenol

HRID 1507278Notes

Reaction equation

HRID 1507278 reaction equation
[F:1][C@H:2]1[C@H:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[C:10]([F:15])[CH:9]=2)[CH2:6][CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.Cl>O1CCOCC1>[F:15][C:10]1[CH:9]=[C:8]([C@@H:7]2[CH2:6][CH2:5][NH:4][CH2:3][C@H:2]2[F:1])[CH:13]=[CH:12][C:11]=1[OH:14]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 118207591(3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidine-1-carboxylate

Product 1

HCID 1182075812-fluoro-4-((3S,4S)-3-fluoropiperidin-4-yl)phenolYield 104.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To (3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidine-1-carboxylate (3.01 g, 9.61 mmol) in dioxane (10 mL) was added HCl (4 M in Dioxane) (24 mL, 96 mmol) and the reaction was allowed to stir at room temperature for 5 h. The reaction was concentrated to an oil. The oil was taken up in saturated aqueous sodium bicarbonate and extracted with EtOAc/5% MeOH. The combined organic layers were concentrated in vacuo to afford 2-fluoro-4-((3S,4S)-3-fluoropiperidin-4-yl)phenol (2.15 g, quantitative yield): LC-MS [M+H]+=214.1; 1H NMR (500 MHz, DMSO-d6) δ 6.93 (d, J=12.4 Hz, 1H), 6.85-6.72 (m, 2H), 4.49 (td, J=9.9, 4.9 Hz, 1H), 4.39 (td, J=10.0, 5.0 Hz, 1H), 3.27-3.19 (m, 3H), 2.85 (d, J=11.4 Hz, 2H), 2.62-2.54 (m, 2H), 2.46-2.37 (m, 4H), 1.76-1.64 (m, 2H), 1.57-1.37 (m, 3H).

Workup

  1. concentrationThe reaction was concentrated to an oil
  2. extractionextracted with EtOAc/5% MeOH
  3. concentrationThe combined organic layers were concentrated in vacuo

Sources & evidence

ORD record
ord-a3bacc72fe834f0ea3a4c0b55560918b
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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