Triethylamine → HCID 11373119, compound

HRID 2120150Notes

Reaction equation

HRID 2120150 reaction equation
[OH:1][C:2]1([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C(N(CC)CC)C.[S:25]1[C:29]2[CH:30]=[CH:31][C:32]([CH2:34][C:35](O)=O)=[CH:33][C:28]=2[CH:27]=[CH:26]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>O1CCCC1.CO.C(OCC)(=O)C.C(Cl)Cl>[OH:1][C:2]1([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:15])[F:16])[CH:9]=2)[CH2:7][CH2:6][N:5]([CH2:35][CH2:34][C:32]2[CH:31]=[CH:30][C:29]3[S:25][CH:26]=[CH:27][C:28]=3[CH:33]=2)[CH2:4][CH2:3]1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 752554-[3-(Trifluoromethyl)phenyl]-4-piperidinolHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11469582Benzo[b]thiophene-5-acetic acid

Product 1

HCID 11373119HCID 11373119, compoundYield 37%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 1.47 g (0.006 mol) of 4-hydroxy-4-(3-trifluoromethylphenyl)piperidine, 30 ml of methylene chloride, 2.25 ml (0.0162 mol) of triethylamine, 1.15 g (0.006 mol) of benzothiophene-5-acetic acid (prepared according to the method described in J. Med. Chem. 1997, 40(7):1049-72) and 2.7 g (0.006 mol) of BOP is stirred at ambient temperature for 3 hours. Ethyl acetate is added to the mixture and the mixture is washed with 1N hydrochloric acid and then with water, with a solution of NaHCO3 and again with water. The organic phase is dried over sodium sulfate and filtered and the solvent is evaporated off. The crude product thus obtained, dissolved in 20 ml of anhydrous tetrahydrofuran (THF), is refluxed for 5 hours and 1.1 ml of a solution of BH3Me2S and 15 ml of anhydrous THF are added thereto. The mixture is cooled to 0° C. and 20 ml of methanol are added thereto dropwise. The mixture is refluxed for 30 minutes, the methanol is evaporated off and the residue is taken up in a 1/1 NH4OH/ethyl acetate mixture. The organic phase is dried over sodium sulfate, filtered and the solvent is evaporated off. The reaction crude is purified by chromatography on a silica gel column, eluting with ethyl acetate. 0.9 g of the title product is obtained.

Workup

  1. customprepared
  2. washthe mixture is washed with 1N hydrochloric acid
  3. dry with materialThe organic phase is dried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent is evaporated off
  6. customThe crude product thus obtained
  7. temperatureis refluxed for 5 hours
  8. temperatureThe mixture is refluxed for 30 minutes
  9. customthe methanol is evaporated off
  10. dry with materialThe organic phase is dried over sodium sulfate
  11. filtrationfiltered
  12. customthe solvent is evaporated off
  13. customThe reaction crude
  14. customis purified by chromatography on a silica gel column
  15. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-8fbc9d47334648e2ad92e5281ea1e067
Source dataset
uspto-grants-2004_02
Patent number
US06689797B2

Reaction notes

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