Piperidine → (2-Bromo-5-phenyl-thiophen-3-yl)-piperidin-1-yl-methanone

HRID 1914542Notes

Reaction equation

HRID 1914542 reaction equation
[Br:1][C:2]1[S:3][C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][C:6]=1[C:7]([OH:9])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=N[C:35]2[CH:36]=[CH:37][CH:38]=[N:39][C:34]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1CCCCC1>CN(C=O)C>[Br:1][C:2]1[S:3][C:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][C:6]=1[C:7]([N:39]1[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38]1)=[O:9]

Participants

6

Reactant 4

HCID 8082PiperidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581103102-Bromo-5-phenylthiophene-3-carboxylic acid

Product 1

HCID 44225122(2-Bromo-5-phenyl-thiophen-3-yl)-piperidin-1-yl-methanoneYield 7.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Bromo-5-phenyl-thiophene-3-carboxylic acid (0.99 g, 3.5 mmol) was dissolved in DMF (20 mL). DIPEA (7.0 mmol), HATU (3.5 mmol) and piperidine (3.5 mmol) were added and the solution stirred at room temperature. The reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid. The organic solution was dried over magnesium sulfate, filtered and the solvent evaporated. The residue was purified by flash chromatography on silica, eluting with 0%-50% ethyl acetate in cyclohexane. The fractions containing the desired product were concentrated under vacuum to give a solid which was further purified by HPLC, eluting with 50%-90% acetonitrile in water (0.1% formic acid) over 30 minutes. The fractions containing the desired product were concentrated under vacuum then freeze-dried to give the title compound (95 mg). LCMS m/z 350.07 [M+H]+ R.T.=12.57 min (Analytical Method 1). 1H NMR (400 MHz, CHCl3-d): δ 7.50 (d, 1H), 7.40 (t, 2H), 7.3 (m, 1H), 7.1 (s, 1H), 3.7 (m, 2H), 3.4 (t, 2H), 1.7 (m, 4 H), 1.6 (m, 2H).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid
  2. dry with materialThe organic solution was dried over magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent evaporated
  5. customThe residue was purified by flash chromatography on silica
  6. washeluting with 0%-50% ethyl acetate in cyclohexane
  7. additionThe fractions containing the desired product
  8. concentrationwere concentrated under vacuum
  9. customto give a solid which
  10. customwas further purified by HPLC
  11. washeluting with 50%-90% acetonitrile in water (0.1% formic acid) over 30 minutes
  12. additionThe fractions containing the desired product
  13. concentrationwere concentrated under vacuum
  14. customthen freeze-dried

Sources & evidence

ORD record
ord-f59f871713214f07a0f9096dbfbebed8
Source dataset
uspto-grants-2013_12
Patent number
US08614209B2

Reaction notes

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