Acetic Acid → HCID 21963151, compound

HRID 2211823Notes

Reaction equation

HRID 2211823 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:36]=[CH:35][CH:34]=[CH:33][C:15]=2[O:16][CH:17]2[CH2:21][CH2:20][N:19]([C:22]3[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=3)[C:18]2=[O:32])[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:37].C=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O.C(OCC)(=O)C.C(=O)(O)[O-].[Na+].O1CCCC1>[ClH:37].[CH3:6][N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:36]=[CH:35][CH:34]=[CH:33][C:15]=2[O:16][CH:17]2[CH2:21][CH2:20][N:19]([C:22]3[CH:23]=[CH:24][C:25]([C:28]([F:29])([F:30])[F:31])=[CH:26][CH:27]=3)[C:18]2=[O:32])[CH2:10][CH2:9]1

Participants

10

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 21963144HCID 21963144, compound

Product 1

HCID 21963151HCID 21963151, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a 50 mL round-bottomed flask equipped with N2 inlet were added 320 mg (0.634 mmol) 3-[2-(4-t-butoxycarbonyl-piperazin-1-yl)-phenoxy]-1-(4-trifluoromethyl-phenyl)-pyrrolidin-2-one and 15 mL dry ethyl acetate. The reaction was saturated with dry HCl and stirred at room temperature for 2 hours. The reaction was evaporated and azeotroped with ether to afford a solid residue that was used directly as follows: To the residue in a 50 mL round-bottomed flask equipped with N2 inlet were added 10 mL dry tetrahydrofuran, 0.109 mL (1.45 mmol) of a 37% solution of formaldehyde in water, 0.041 mL (0.723 mmol) acetic acid, and 306 mg (1.45 mmol) sodium triacetoxyborohydride. The reaction was stirred at room temperature overnight, then diluted with ethyl acetate and saturated aqueous sodium bicarbonate solution. The layers were separated, and the aqueous layer was washed three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, and evaporated. The residue was dissolved in ethyl acetate and the product extracted into 1N aqueous HCl; then the aqueous layer, after washing 2 times with ethyl acetate, was basified with solid potassium carbonate and extracted 3 times with ethyl acetate. The organic layer was dried over magnesium sulfate and evaporated. The resulting oil was dissolved in ethyl acetate and treated with 2 mL of a solution of ethyl acetate saturated with HCl, then evaporated to a solid, 37 mg (13%), mp 137–162° C.

Workup

  1. customTo a 50 mL round-bottomed flask equipped with N2 inlet
  2. customThe reaction was evaporated
  3. customazeotroped with ether
  4. customto afford a solid residue that
  5. customTo the residue in a 50 mL round-bottomed flask equipped with N2 inlet
  6. stirringThe reaction was stirred at room temperature overnight
  7. customThe layers were separated
  8. washthe aqueous layer was washed three times with ethyl acetate
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over magnesium sulfate
  11. customevaporated
  12. dissolutionThe residue was dissolved in ethyl acetate
  13. extractionthe product extracted into 1N aqueous HCl
  14. washthen the aqueous layer, after washing 2 times with ethyl acetate
  15. extractionextracted 3 times with ethyl acetate
  16. dry with materialThe organic layer was dried over magnesium sulfate
  17. customevaporated
  18. dissolutionThe resulting oil was dissolved in ethyl acetate
  19. additiontreated with 2 mL of a solution of ethyl acetate saturated with HCl
  20. customevaporated to a solid, 37 mg (13%), mp 137–162° C.

Sources & evidence

ORD record
ord-302b7bae986449b58a90280643d8e300
Source dataset
uspto-grants-2006_09
Patent number
US07101885B2

Reaction notes

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