Ethyl Acetate → HCID 21919402, compound

HRID 1581947Notes

Reaction equation

HRID 1581947 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:28][C:29]1[CH:30]=[C:31]([CH2:35][CH2:36][C:37](OCC)=[O:38])[CH:32]=[N:33][CH:34]=1.C(OCC)(=O)C>C1COCC1.CCCCCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([CH2:17][C:37](=[O:38])[CH2:36][CH2:35][C:31]3[CH:32]=[N:33][CH:34]=[C:29]([Cl:28])[CH:30]=3)(=[O:15])=[O:16])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 2733832Lithium HexamethyldisilazideHCID 4157412HCID 4157412, compoundHCID 21919385HCID 21919385, compound

Product 1

HCID 21919402HCID 21919402, compoundYield 61.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

To a stirred solution of 1-(4-chlorophenyl)-4-(methylsulfonyl)piperazine (235 mg, 0.85 mmol) in dry THF (7.5 mL) at −10° C. under an argon atmosphere was added dropwise over 4 minutes a solution of LiHMDS (1.71 mL of a 1.0 M solution in THF, 1.71 mmol). The solution was then stirred at this temperature for 40 minutes. A solution of ethyl 3-(5-chloropyridin-3-yl)propanoate (201 mg, 0.94 mmol) in THF (1 mL) was then added dropwise via cannula over a period of 5 minutes. The reaction was stirred at −10° C. for an additional 30 minutes before being quenched with saturated aqueous ammonium chloride solution (5 mL). Volatiles were removed in vacuo, and the residue was extracted with CH2Cl2 (3×5 mL). The combined organic extracts were washed with water (10 mL) and brine (10 mL) before being dried, (MgSO4), filtered and concentrated in vacuo. Flash chromatography (silica gel, 50% ethyl acetate in hexane) gave the title compound (228 mg, 0.52 mmol) and recovered ethyl 3-(5-chloropyridin-3-yl)propanoate (74 mg, 0.35 mmol).

Workup

  1. stirringThe reaction was stirred at −10° C. for an additional 30 minutes
  2. custombefore being quenched with saturated aqueous ammonium chloride solution (5 mL)
  3. customVolatiles were removed in vacuo
  4. extractionthe residue was extracted with CH2Cl2 (3×5 mL)
  5. washThe combined organic extracts were washed with water (10 mL) and brine (10 mL)
  6. dry with materialbefore being dried, (MgSO4),
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7a5b3b8a894f43df9621b053e244b8f9
Source dataset
uspto-grants-2004_05
Patent number
US06734183B2

Reaction notes

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