4-Fluorobenzoyl chloride → HCID 11290310, compound

HRID 1661169Notes

Reaction equation

HRID 1661169 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]#[C:10][CH:11]2[CH2:16][CH2:15][CH2:14][NH:13][CH2:12]2)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.[F:26][C:27]1[CH:35]=[CH:34][C:30]([C:31](Cl)=[O:32])=[CH:29][CH:28]=1>C1COCC1>[F:26][C:27]1[CH:35]=[CH:34][C:30]([C:31]([N:13]2[CH2:14][CH2:15][CH2:16][CH:11]([C:10]#[C:9][C:6]3[CH:7]=[CH:8][C:3]([F:2])=[CH:4][CH:5]=3)[CH2:12]2)=[O:32])=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 678794-Fluorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 66618608HCID 66618608, compound

Product 1

HCID 11290310HCID 11290310, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 3-(4-Fluoro-phenylethynyl)-piperidine hydrochloride (0.14 g, 0.58 mmol) in THF (2.3 ml, 0.5M) was added DIEA (0.5 ml, 2.92 mmol). The reaction mixture was cooled to 0° C. and 4-Fluoro-benzoyl chloride (0.139 g-0.87 mmol) was slowly added. The reaction was to go up to R.T and stirred for 24 h. The solution was concentrated and DCM was added following by HCl 1N. The aqueous phase was separated and organic phase was extracted twice with HCl 1N and twice with water, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (DCM/MeOH:98/2) to afford 0.86 mg (45%) of (4-Fluoro-phenyl)-[3-(4-fluoro-phenylethynyl)-piperidin-1-yl]-methanone as a brown oil. Rf=0.39 (DCM/MeOH:98/2); LCMS (Tr): 4.14 min (Method C); MS (ES+) gave m/z: 326.2; 1H-NMR (CDCl3), δ (ppm): 8.10 (d, 2H), 7.60 (d, 2H), 7.15 (d, 2H), 6.94 (d, 2H), 3.47-3.30 (m, 4H), 2.54 (m, H), 1.63-1.50 (m, 4H).

Workup

  1. concentrationThe solution was concentrated
  2. additionDCM was added
  3. customThe aqueous phase was separated
  4. extractionorganic phase was extracted twice with HCl 1N and twice with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography (DCM/MeOH:98/2)

Sources & evidence

ORD record
ord-48f75454f9264bb1bf9d3da02be1fc95
Source dataset
uspto-grants-2011_10
Patent number
US08030331B2

Reaction notes

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