Water → HCID 22845913, compound

HRID 1885991Notes

Reaction equation

HRID 1885991 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C)P(=O)(N(C)C)N(C)C.[CH2-]C(C)=O.Br[CH2:35][CH2:36][C@H:37](O)[CH2:38][OH:39].O>O1CCCC1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C@H:15]2[CH2:35][CH2:36][C@@H:37]([CH2:38][OH:39])[O:18][C:16]2=[O:17])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 12679HexamethylphosphoramideHCID 810334-Benzyloxyphenylacetic acidHCID 178521077HCID 178521077, compound

Product 1

HCID 22845913HCID 22845913, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

In 2 ml of tetrahydrofuran was dissolved 1.01 g (10 millimoles) of diisopropyl amine, and 6.5 ml of 14.5% solution of n-butyl lithium in hexane was added to the solution to form lithium diisopropylamine. The solution was cooled to -20° C. and a solution of 1.21 g (5 millimoles) of 4-benzyloxyphenylacetic acid in 5 ml of tetrahydrofuran was added dropwise into the solution. Then 3 ml of hexamethyl phosphorictriamide was added to the mixture, and reaction was carried out at a temperature maintained at -5° to 0° C. with stirring for 30 minutes. The obtained di-anion solution was cooled to -30° C., and 2.3 g (9.6 millimoles) of (S)-4-bromo-1,2-butanediol acetonide was added dropwise into the solution. After the dropwise addition, the mixture was stirred for 2 hours at a temperature controlled to 10° to 20° C. Then, water was added to the mixture, tetrahydrofuran was removed by distillation, and the residue was neutralized with dilute hydrochloric acid. The reaction product was extracted from the solution with chloroform, and the extract was washed with water and dried over magnesium sulfate. The solvent was removed under a reduced pressure. The obtained product was purified by the silica gel column chromatography to obtain purified (2R,5S)-2-(4-benzyloxyphenyl)-5-hydroxymethyl-δ-valerolactone.

Workup

  1. temperaturemaintained at -5° to 0° C.
  2. temperatureThe obtained di-anion solution was cooled to -30° C.
  3. additionAfter the dropwise addition
  4. stirringthe mixture was stirred for 2 hours at a temperature
  5. customcontrolled to 10° to 20° C
  6. customwas removed by distillation
  7. extractionThe reaction product was extracted from the solution with chloroform
  8. washthe extract was washed with water
  9. dry with materialdried over magnesium sulfate
  10. customThe solvent was removed under a reduced pressure
  11. customThe obtained product was purified by the silica gel column chromatography
  12. customto obtain
  13. custompurified (2R,5S)-2-(4-benzyloxyphenyl)-5-hydroxymethyl-δ-valerolactone

Sources & evidence

ORD record
ord-c63a2b3c28a44dc69d3b4920c5a1dc21
Source dataset
uspto-grants-1992_09
Patent number
US05149462

Reaction notes

Loading…