Acetic Acid → HCID 54472112, compound

HRID 326944Notes

Reaction equation

HRID 326944 reaction equation
C[Mg]Cl.[C:4]1(C)C=CC=CC=1.[F:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][C:21]=1[F:22])[N:18]=[C:17]([CH:23]=[CH:24][C:25]1[CH:26]=[C:27]([C@@H:31]([OH:45])[CH2:32][CH2:33][C:34]3[CH:44]=[CH:43][CH:42]=[CH:41][C:35]=3C(OCC)=O)[CH:28]=[CH:29][CH:30]=1)[CH:16]=[CH:15]2.[CH3:46][C:47]([OH:49])=O>C1COCC1>[F:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][C:21]=1[F:22])[N:18]=[C:17]([CH:23]=[CH:24][C:25]1[CH:26]=[C:27]([C@@H:31]([OH:45])[CH2:32][CH2:33][C:34]3[CH:44]=[CH:43][CH:42]=[CH:41][C:35]=3[C:47]([OH:49])([CH3:46])[CH3:4])[CH:28]=[CH:29][CH:30]=1)[CH:16]=[CH:15]2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1140Toluene2×HCID 54270075HCID 54270075, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 54472112HCID 54472112, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of anhydrous CeCl3 (40.5 g, 164 mmol) in THF (500 mL) was refluxed overnight using a Dean Stark trap filled with activated 3 Å molecular sieves. Methyl magnesium chloride (263 mL, 3.0 Molar in THF, 790 mmol) was added dropwise over 30 minutes to the CeCl3 slurry at 0° C. After stirring 2 hours at 0° C., the mixture was cooled to -5° C. and a toluene (600 mL) solution of the hydroxyester (71.8 g, 152 mmol) from Step 5 was added dropwise over 1 hour. The reaction mixture was stirred another hour before the addition of 2M HOAc (600 mL) and toluene (600 mL). The organic layer was washed with saturated aq. NaHCO3 and with brine. Concentration in vacuo and purification of the residue by flash chromatography (30% EtOAc in toluene) gave 63.48 g (91%) of the title compound.

Workup

  1. temperaturewas refluxed overnight
  2. additionfilled with activated 3 Å molecular sieves
  3. temperaturethe mixture was cooled to -5° C.
  4. washThe organic layer was washed with saturated aq. NaHCO3 and with brine
  5. concentrationConcentration
  6. customin vacuo and purification of the residue by flash chromatography (30% EtOAc in toluene)

Sources & evidence

ORD record
ord-12397d09f7fc4250a024ab03fbcefa99
Source dataset
uspto-grants-1993_12
Patent number
US05270324

Reaction notes

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