(2R)-3-Chloro-1,2-propanediol → HCID 25074250, compound

HRID 2047310Notes

Reaction equation

HRID 2047310 reaction equation
[CH2:1]([N:3]([CH3:25])[C:4]1[CH:9]=[C:8]([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:20]=[C:19]([CH3:21])[C:18]([OH:22])=[C:17]([CH3:23])[CH:16]=3)[N:11]=2)[CH:7]=[C:6]([CH3:24])[N:5]=1)[CH3:2].Cl[CH2:27][C@H:28]([OH:31])[CH2:29][OH:30]>C(O)(C)C.[OH-].[Na+].CC(=O)OCC>[CH2:1]([N:3]([CH3:25])[C:4]1[CH:9]=[C:8]([C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:20]=[C:19]([CH3:21])[C:18]([O:22][CH2:27][C@H:28]([OH:31])[CH2:29][OH:30])=[C:17]([CH3:23])[CH:16]=3)[N:11]=2)[CH:7]=[C:6]([CH3:24])[N:5]=1)[CH3:2]

Participants

6

Reactant 2

HCID 148793(2R)-3-Chloro-1,2-propanediol3×HCID 136375863HCID 136375863, compound

Product 1

HCID 25074250HCID 25074250, compoundYield 37.2%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 4-{5-[2-(ethyl-methyl-amino)-6-methyl-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-2,6-dimethyl-phenol (55 mg, 0.163 mmol) in isopropanol (3 mL) and 3 N aq. NaOH (0.5 mL), (R)-3-chloro-1,2-propanediol (98 mg, 0.894 mmol) is added. The mixture is stirred at 65° C. for 72 h before another portion of (R)-3-chloro-1,2-propanediol (98 mg, 0.894 mmol) is added. Stirring is continued at 65° C. for 4 days before a third portion of (R)-3-chloro-1,2-propanediol (98 mg, 0.894 mmol) is added. After stirring for another 48 h, the mixture is diluted with EA (50 mL) and washed with 1 N aq. NaOH (10 mL) followed by brine (10 mL), dried over MgSO4, filtered and concentrated. The crude product is purified on prep. TLC plates with DCM containing 10% of 7 N NH3 in methanol and 5% of methanol to give (R)-3-(4-{5-[2-(ethyl-methyl-amino)-6-methyl-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-2,6-dimethyl-phenoxy)-propane-1,2-diol (25 mg) as a yellow solid; LC-MS: tR=0.73 min; [M+1]+=413.14.

Workup

  1. additionis added
  2. additionis added
  3. stirringAfter stirring for another 48 h
  4. washwashed with 1 N aq. NaOH (10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is purified on prep

Sources & evidence

ORD record
ord-5000b26c313d4f91b3b84bda56cc57cc
Source dataset
uspto-grants-2013_11
Patent number
US08592460B2

Reaction notes

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