2-Phenylthiophene → HCID 19705288, compound

HRID 727095Notes

Reaction equation

HRID 727095 reaction equation
[C:1]1([C:7]2[S:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18]>O1CCCC1>[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27]([OH:30])([C:9]2[S:8][C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:11][CH:10]=2)[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 699992-PhenylthiopheneHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 19705288HCID 19705288, compoundYield 76.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a solution of 2-phenylthiophene (1.35 g, 9.1 mmol) in tetrahydrofuran (40 ml) at -40° C. under a nitrogen atmosphere was added a solution of n-butyllithium (1.6M in hexanes, 6 ml, 95 mmol) keeping the temperature below -40° C. The reaction was stirred at -40° C. for 10 minutes, allowed to warm to 0° C. and stirred at 0° C. for 30 minutes. The reaction was cooled to -78° C. and a solution of 1-tert-butoxycarbonyl-4-piperidone (1.8 g, 9.1 mmol) in tetrahydrofuran (20 ml) added, keeping the temperature below -50° C. When addition was complete, the reaction was stirred at -60° C. for 30 minutes and at room temperature for 1 hour. The reaction was cooled to 0° C. and quenched by addition of saturated aqueous ammonium chloride (10 ml), poured into water (100 ml) and extracted with ethyl acetate (3×50 ml). The combined extracts were washed with brine (50 ml), dried (MgSO4) and evaporated in vacuo to an oil. Purification by chromatography on silica eluting with ethyl acetate/hexane (1:2) gave the title compound as a foam, (2.5 g, 76%). δH (CDCl3) 1.41 (9H, s, OC(CH3)3), 1.84-1.97 (2H, m, piperidinyl H), 2.36 (1H, t, J 9.0 Hz, piperidinyl H), 3.20-3.28 (2H, m, piperidinyl H), 3.64 (1H, t, J 8.9 Hz, piperidinyl H), 3.82 (2H, m, piperidinyl H), 6.86-6.91 (1H, m, ArH), 7.09 (1H, m, ArH), 7.09 (1H, d, J 5.3 Hz, ArH), 7.16-7.33 (3H, m, ArH), 7.46-7.51 (2H, m, ArH).

Workup

  1. customthe temperature below -40° C
  2. temperatureto warm to 0° C.
  3. stirringstirred at 0° C. for 30 minutes
  4. temperatureThe reaction was cooled to -78° C.
  5. customthe temperature below -50° C
  6. additionWhen addition
  7. stirringthe reaction was stirred at -60° C. for 30 minutes and at room temperature for 1 hour
  8. temperatureThe reaction was cooled to 0° C.
  9. customquenched by addition of saturated aqueous ammonium chloride (10 ml)
  10. additionpoured into water (100 ml)
  11. extractionextracted with ethyl acetate (3×50 ml)
  12. washThe combined extracts were washed with brine (50 ml)
  13. dry with materialdried (MgSO4)
  14. customevaporated in vacuo to an oil
  15. customPurification by chromatography on silica eluting with ethyl acetate/hexane (1:2)

Sources & evidence

ORD record
ord-ad87e33cafaa415583197121f51514ca
Source dataset
uspto-grants-1998_01
Patent number
US05712285

Reaction notes

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