(3S,4S)-tert-butyl 4-(4-(benzyloxy)-3-fluorophenyl)-3-hydroxypiperidine-1-carboxylate → (3S,4S)-tert-butyl 4-(3-fluoro-4-hydroxyphenyl)-3-hydroxypiperidine-1-carboxylate

HRID 1507276Notes

Reaction equation

HRID 1507276 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][C@H:16]2[OH:28])=[CH:11][C:10]=1[F:29])C1C=CC=CC=1>CO.[Pd]>[F:29][C:10]1[CH:11]=[C:12]([C@@H:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:17][C@H:16]2[OH:28])[CH:13]=[CH:14][C:9]=1[OH:8]

Participants

4

Reactant 1

HCID 118207305(3S,4S)-tert-butyl 4-(4-(benzyloxy)-3-fluorophenyl)-3-hydroxypiperidine-1-carboxylate

Product 1

HCID 118207420(3S,4S)-tert-butyl 4-(3-fluoro-4-hydroxyphenyl)-3-hydroxypiperidine-1-carboxylateYield 96.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To (3S,4S)-tert-butyl 4-(4-(benzyloxy)-3-fluorophenyl)-3-hydroxypiperidine-1-carboxylate (4.0 g, 9.96 mmol, E-2 from step C) in degassed MeOH (100 mL) was added 10% Pd/C (0.191 g, 1.79 mmol) and the reaction was repeated evacuated and flushed with hydrogen gas. Then placed under 1 atm of hydrogen for 4 h. The reaction solution was purged with nitrogen and filtered through celite. The filtrated was concentrated to afford (3S,4S)-tert-butyl 4-(3-fluoro-4-hydroxyphenyl)-3-hydroxypiperidine-1-carboxylate (2.99 g, 96% yield) as a grey oil. LC-MS [M+H]+−tBu=256.05; 1H NMR (500 MHz, DMSO-d6) δ 7.03-6.95 (m, 1H), 6.89-6.78 (m, 2H), 4.78 (d, J=4.6 Hz, 1H), 4.09 (br. s., 2H), 3.94 (br. s., 1H), 3.36 (dd, J=9.5, 4.7 Hz, 1H), 3.17 (s, 1H), 2.80-2.58 (m, 1H), 2.42-2.27 (m, 1H), 1.65 (dd, J=13.4, 3.4 Hz, 1H), 1.56-1.33 (m, 10H).

Workup

  1. customthe reaction was repeated evacuated
  2. customflushed with hydrogen gas
  3. customThe reaction solution was purged with nitrogen
  4. filtrationfiltered through celite
  5. concentrationThe filtrated was concentrated

Sources & evidence

ORD record
ord-9516f5f2b104490e8336ac19765ec707
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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