Water → HCID 14576266, compound

HRID 1956776Notes

Reaction equation

HRID 1956776 reaction equation
CC(C)([O-])C.[K+].[C:7]([O:15]C)(=O)[C:8]1[CH:13]=[CH:12][CH:11]=[N:10][CH:9]=1.C1(=O)[O:22][CH2:21][CH2:20][CH2:19][CH2:18]1.O>O1CCCC1>[N:10]1[CH:11]=[CH:12][CH:13]=[C:8]([C:7]([CH2:18][CH2:19][CH2:20][CH2:21][OH:22])=[O:15])[CH:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7151Methyl NicotinateHCID 10953Delta-ValerolactoneHCID 23665647Potassium tert-butoxide

Product 1

HCID 14576266HCID 14576266, compoundYield 54.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A stirred solution of potassium tert-butoxide (83.55 g) in tetrahydrofuran (500 ml) under nitrogen at room temperature is treated with a solution of methyl nicotinate (68.5 g) and delta-valerolactone (75.0 g) in tetrahydrofuran (125 ml), continuously during 1 hour, maintaining the temperature between 22° C. and 32° C. The mixture is stirred for 2 hours and is then treated with water (750ml). The resulting mixture is washed with xylene (125 ml) and the aqueous layer is then treated with concentrated hydrochloric acid (400 ml) during a period of 15 minutes, maintaining the temperature between 23° C. and 44° C. The solution is stirred for 90 minutes and then the solution is washed with dichloromethane (250 ml). The aqueous layer is basified to pH8-pH9 by treatment with aqueous sodium hydroxide solution (specific gravity 1.3;480 ml) and then it is washed with xylene* (125 ml) and extracted with dichloromethane (3×250 ml). The combined dichloromethane extracts are dried over magnesium sulphate and the solvent is removed by evaporation under reduced pressure, to give 4-hydroxybutyl 3-pyridyl ketone (49.1 g), in the form of a yellow oil which crystallises to form a pale brown solid, m.p. 36°-38° C. [NMR (CDCl3): 1.7(m,2H), 1.9(m,2H), 3.1(t,2H),3.7(t,2H),7.4(m,1H),8.2(dt,1H),8.8(m,1H), 9.2(m,1H)].

Workup

  1. temperaturemaintaining the temperature between 22° C. and 32° C
  2. washThe resulting mixture is washed with xylene (125 ml)
  3. additionthe aqueous layer is then treated with concentrated hydrochloric acid (400 ml) during a period of 15 minutes
  4. temperaturemaintaining the temperature between 23° C. and 44° C
  5. stirringThe solution is stirred for 90 minutes
  6. washthe solution is washed with dichloromethane (250 ml)
  7. washit is washed with xylene* (125 ml)
  8. extractionextracted with dichloromethane (3×250 ml)
  9. dry with materialThe combined dichloromethane extracts are dried over magnesium sulphate
  10. customthe solvent is removed by evaporation under reduced pressure

Sources & evidence

ORD record
ord-f1707289e9774f63b05a5650bc339ff8
Source dataset
uspto-grants-1998_07
Patent number
US05780636

Reaction notes

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