(Diethylamino)sulfur trifluoride → 4-(4-Bromophenyl)-4-fluoro-1-methylpiperidine

HRID 447315Notes

Reaction equation

HRID 447315 reaction equation
CCN(S(F)(F)[F:7])CC.[Br:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2(O)[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)=[CH:13][CH:12]=1.BrC1C=CC(C2CCN(C)CC=2)=CC=1>C(Cl)Cl>[Br:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2([F:7])[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]2)=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 106345354-(4-bromophenyl)-1-methyl-3,6-dihydro-2H-pyridineHCID 106596344-(4-Bromophenyl)-1-methylpiperidin-4-ol

Product 1

HCID 582665264-(4-Bromophenyl)-4-fluoro-1-methylpiperidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of DAST (0.50 g, 3.8 mmol) in CH2Cl2 was added a solution of 4-(4-bromophenyl)-1-methylpiperidin-4-ol (0.507 g, 1.88 mmol) in CH2Cl2 at −78° C. The resulting mixture was warmed to rt over a period of 3 h. The reaction was then allowed to cool to 0° C. and quenched with saturated NaHCO3. The resulting mixture was extracted with CH2Cl2 and the combined organic extracts were dried over MgSO4 and concentrated to give a yellow oil. The crude product was purified by silica gel chromatography (95:5 EtOAc/NH3 to 10:8:2 CH2Cl2/MeOH/NH3) to yield an inseparable mixture of the title compound and 4-(4-bromophenyl)-1-methyl-1,2,3,6-tetrahydropyridine (280 mg, used without further purification).

Workup

  1. temperatureto cool to 0° C.
  2. customquenched with saturated NaHCO3
  3. extractionThe resulting mixture was extracted with CH2Cl2
  4. dry with materialthe combined organic extracts were dried over MgSO4
  5. concentrationconcentrated
  6. customto give a yellow oil
  7. customThe crude product was purified by silica gel chromatography (95:5 EtOAc/NH3 to 10:8:2 CH2Cl2/MeOH/NH3)
  8. customto yield

Sources & evidence

ORD record
ord-17e338c6fa76401785325169d3939b77
Source dataset
uspto-grants-2013_07
Patent number
US08481533B2

Reaction notes

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