Sodium → (S)-1-(4-chloro-3-fluorophenyl)propane-1,3-diol

HRID 1774159Notes

Reaction equation

HRID 1774159 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[O:10][C@@H:9]2[CH2:11][OH:12])=[CH:4][C:3]=1[F:13].[Na].[H-].[Al+3].[H-].[H-]>COCCOC.CCOCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([OH:10])[CH2:9][CH2:11][OH:12])=[CH:4][C:3]=1[F:13]

Participants

6

Reactant 3

HCID 5360545SodiumHCID 21584524AluminiumhydrideHCID 86696658((2R,3R)-3-(4-chloro-3-fluorophenyl)oxiran-2-yl)methanol

Product 1

HCID 86696659(S)-1-(4-chloro-3-fluorophenyl)propane-1,3-diolYield 98.55%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
0 °C

Procedure

((2R,3R)-3-(4-Chloro-3-fluorophenyl)oxiran-2-yl)methanol (10.55 g, 52.07 mmol) was dissolved in 1,2-dimethoxyethane (150 mL) and cooled to 0° C. Sodium bis (2-methohyethoxy) aluminum hydride (“Red-Al”) (17.46 mL, 57.28 mmol) was added dropwise. The mixture was agitated for 3 hours at room temperature, diluted with ether (250 mL) and quenched with HCl solution (20 mL, 6M HCl+60 mL water). After agitating for 30 minutes, the aqueous phase was separated and extracted twice with ethyl acetate. The combined organics were washed with brine, dried with MgSO4, and evaporated to give (S)-1-(4-chloro-3-fluorophenyl)propane-1,3-diol (10.5 g, 51.31 mmol, 98.55% yield) as thick oil.

Workup

  1. customquenched with HCl solution (20 mL, 6M HCl+60 mL water)
  2. stirringAfter agitating for 30 minutes
  3. customthe aqueous phase was separated
  4. extractionextracted twice with ethyl acetate
  5. washThe combined organics were washed with brine
  6. dry with materialdried with MgSO4
  7. customevaporated

Sources & evidence

ORD record
ord-bb596d66141a4fa2a27ee9b16fc2818f
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

Loading…