n-(4-Bromophenyl)prop-2-enamide → 3-[4-(3-benzyloxyphenyl)-4-fluoropiperidin-1-yl]-N-(4-bromophenyl)propionamide hydrochloride

HRID 537225Notes

Reaction equation

HRID 537225 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:12])[CH:10]=[CH2:11])=[CH:4][CH:3]=1.[ClH:13].[CH2:14]([O:21][C:22]1[CH:23]=[C:24]([C:28]2([F:34])[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[CH:25]=[CH:26][CH:27]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)(O)[O-].[Na+]>CO>[ClH:13].[CH2:14]([O:21][C:22]1[CH:23]=[C:24]([C:28]2([F:34])[CH2:29][CH2:30][N:31]([CH2:11][CH2:10][C:9]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=3)=[O:12])[CH2:32][CH2:33]2)[CH:25]=[CH:26][CH:27]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 263609n-(4-Bromophenyl)prop-2-enamideHCID 516892Sodium BicarbonateHCID 674607714-(3-benzyloxyphenyl)-4-fluoropiperidine Hydrochloride

Product 1

HCID 674617753-[4-(3-benzyloxyphenyl)-4-fluoropiperidin-1-yl]-N-(4-bromophenyl)propionamide hydrochlorideYield 64%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of N-(4-bromophenyl)acrylamide (340 mg, 1.50 mmol) in methanol (10 mL) was added 4-(3-benzyloxyphenyl)-4-fluoropiperidine hydrochloride (321 mg, 1.00 mmol) followed by sodium bicarbonate (840 mg, 10.0 mmol) and the resulting suspension stirred at room temperature for 52 hours. After this time the reaction was filtered and the filtrate concentrated under reduced pressure. The residue was treated with ethyl acetate (10 mL) and the resulting suspension re-filtered and concentrated under reduced pressure. The resulting solid was treated with 10% hydrogen chloride in methanol (10 mL) and the solution re-concentrated. Subsequent trituration with ethyl acetate (10 mL) afforded 3-[4-(3-benzyloxyphenyl)-4-fluoropiperidin-1-yl]-N-(4-bromophenyl)propionamide hydrochloride in 64% yield as a light yellow solid.

Workup

  1. filtrationAfter this time the reaction was filtered
  2. concentrationthe filtrate concentrated under reduced pressure
  3. additionThe residue was treated with ethyl acetate (10 mL)
  4. filtrationthe resulting suspension re-filtered
  5. concentrationconcentrated under reduced pressure
  6. additionThe resulting solid was treated with 10% hydrogen chloride in methanol (10 mL)
  7. concentrationthe solution re-concentrated

Sources & evidence

ORD record
ord-8dcabcc24d604ce78aa2354401738971
Source dataset
uspto-grants-2014_10
Patent number
US08859777B2

Reaction notes

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