Malic Acid → HCID 19768421, compound

HRID 1590850Notes

Reaction equation

HRID 1590850 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH:23](O)[CH2:24][CH2:25][O:26][CH2:27][CH2:28][CH3:29])=[CH:17][C:16]=2[F:31])=[N:13][CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].O1C(CCOCCC)C1.C(O)(=O)C(CC(O)=O)O.C(OC1C=CC(C2C=CC(O)=CC=2[F:71])=NC=1)CCCCCC.CCN(S(F)(F)F)CC>C(=O)([O-])[O-].[K+].[K+].C(C(C)=O)C.C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH:23]([F:71])[CH2:24][CH2:25][O:26][CH2:27][CH2:28][CH3:29])=[CH:17][C:16]=2[F:31])=[N:13][CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]

Participants

9

Reactant 5

HCID 525Malic AcidHCID 123472(Diethylamino)sulfur trifluorideHCID 19768417HCID 19768417, compoundHCID 20087472HCID 20087472, compoundHCID 135827543HCID 135827543, compound

Product 1

HCID 19768421HCID 19768421, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 6569Methyl Ethyl KetoneSolventHCID 11430Potassium CarbonateSolvent

Procedure

A solution of 0.1 mol of 5-heptyloxy-2-(4-(2-hydroxy-5-oxaoctyloxy)-2-fluorophenyl)pyridine (prepared by heating optically active 1,2-epoxy-5-oxaoctane, obtainable from malic acid, with 5-heptyloxy-2-(4-hydroxy-2-fluorophenyl)pyridine in the presence of dry potassium carbonate and methyl ethyl ketone as solvent) in methylene chloride is cooled to -40° C. and 0.11 mol of DAST is added to it dropwise with moisture being excluded. The reaction mixture is then stirred for 12 hours while heating slowly to room temperature. Then hydrolysis is carried out with ice cooling and the reaction mixture is washed with dilute sodium hydroxide solution and several times with water. After drying over magnesium sulfate, the solvent is removed on a rotary evaporator and the crude product is purified chromatographically and - by crystallization. Optically active 5-heptyloxy-2-(4-(2-fluoro-5-oxaoctyloxy)-2-fluorophenyl)pyridine is obtained.

Workup

  1. customThen hydrolysis
  2. washthe reaction mixture is washed with dilute sodium hydroxide solution and several times with water
  3. dry with materialAfter drying over magnesium sulfate
  4. customthe solvent is removed on a rotary evaporator
  5. customthe crude product is purified chromatographically and - by crystallization

Sources & evidence

ORD record
ord-e719c0df00274ef3912b11a0240e50ac
Source dataset
uspto-grants-1993_04
Patent number
US05204476

Reaction notes

Loading…