(Diethylamino)sulfur trifluoride → (3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidine-1-carboxylate

HRID 1507277Notes

Reaction equation

HRID 1507277 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][C@H:10]2O)[CH:5]=[CH:6][C:7]=1[OH:8].CCN(S(F)(F)[F:29])CC>C(Cl)Cl>[F:29][C@H:10]1[C@H:9]([C:4]2[CH:5]=[CH:6][C:7]([OH:8])=[C:2]([F:1])[CH:3]=2)[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11]1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 118207420(3S,4S)-tert-butyl 4-(3-fluoro-4-hydroxyphenyl)-3-hydroxypiperidine-1-carboxylate

Product 1

HCID 118207591(3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidine-1-carboxylateYield 129%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (3S,4S)-tert-butyl 4-(3-fluoro-4-hydroxyphenyl)-3-hydroxypiperidine-1-carboxylate (2.99 g, 9.60 mmol) in DCM (75 mL) at 0° C. was added DAST (6.34 mL, 48.0 mmol) dropwise. The reaction was then allowed to warm to room temperature and stir for 2 h. The reaction was slowly quenched with ice water. The reaction was then extracted with dichloromethane, washed with additional water, dried with magnesium sulfate, filtered and concentrated in vacuo to afford (3S,4S)-tert-butyl 3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidine-1-carboxylate (3.88 g, quantitative yield) as a yellow viscous oil: LC-MS [M−H]+ 312.2; 1H NMR (500 MHz, DMSO-d6) δ 7.22-7.10 (m, 1H), 7.00-6.76 (m, 3H), 5.76 (s, 2H), 4.60 (td, J=10.1, 5.2 Hz, 1H), 4.50 (td, J=10.1, 5.2 Hz, 1H), 4.27 (br. s., 1H), 4.07-3.78 (m, 2H), 3.66-3.50 (m, 1H), 3.00-2.65 (m, 4H), 1.81-1.69 (m, 1H), 1.63-1.50 (m, 1H), 1.46-1.30 (m, 14H), 1.20-1.01 (m, 2H).

Workup

  1. customThe reaction was slowly quenched with ice water
  2. extractionThe reaction was then extracted with dichloromethane
  3. washwashed with additional water
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-75d8da51abfc47c99fedab9cef2f679a
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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