Chloroform → HCID 15294933, compound

HRID 1757598Notes

Reaction equation

HRID 1757598 reaction equation
P(Cl)(Cl)(Cl)=O.C(Cl)(Cl)Cl.[CH3:10][O:11][C:12]1[C:30]([O:31][CH3:32])=[CH:29][C:15]([CH2:16][CH2:17][NH:18][C:19](=O)[CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[CH:14][C:13]=1[OH:33].[BH4-].[Na+]>CO>[CH3:32][O:31][C:30]1[CH:29]=[C:15]2[C:14](=[C:13]([OH:33])[C:12]=1[O:11][CH3:10])[CH:19]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[NH:18][CH2:17][CH2:16]2

Participants

6

Reactant 4

HCID 6212ChloroformHCID 24813Phosphorus oxychlorideHCID 4311764Sodium borohydrideHCID 15341358HCID 15341358, compound

Product 1

HCID 15294933HCID 15294933, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
55 °C

Procedure

Phosphoryl chloride (370 μl, 3.97 mmol) was added to a chloroform (6 ml)solution of N-(4,5-dimethoxy-3-hydroxyphenethyl)-4-fluorophenylacetamide (437 mg, 1.31 mmol) at room temperature, and the mixture was stirred undera nitrogen atmosphere at 55° C. for 8 hours. The solvent and the excess phosphoryl chloride were removed under reduced pressure and the resultant residue was dissolved in methanol (25 ml). Sodium borohydride (65 mg, 1.72 mmol) was added to this methanol solution under ice cooling and the mixture was stirred for 1 hour. The solvent was removed under reduced pressure, brine (50 ml) was added to the resultant residue, and the mixture was extracted three times with chloroform (30 ml). The organiclayer was dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure, and the resultant residue was recrystallized from ethyl acetate-hexane to give 199 mg (yield: 48%) of the captioned compoundas a colorless solid. Melting point: 195°-200° C. FAB-MS (m/z, (C18H20NO3F+H)+): 318 1H-NMR (300MHz, CD3OD, δ ppm): 2.97-3.08 (3H, m), 3.22-3.34 (1H, m), 3.46-3.55(2H, m), 3.78 (3H,(2H, m), 7.34-7.38 (2H, m)

Workup

  1. customThe solvent and the excess phosphoryl chloride were removed under reduced pressure
  2. dissolutionthe resultant residue was dissolved in methanol (25 ml)
  3. stirringthe mixture was stirred for 1 hour
  4. customThe solvent was removed under reduced pressure, brine (50 ml)
  5. additionwas added to the resultant residue
  6. extractionthe mixture was extracted three times with chloroform (30 ml)
  7. dry with materialThe organiclayer was dried over anhydrous magnesium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customthe resultant residue was recrystallized from ethyl acetate-hexane
  10. customto give 199 mg (yield: 48%) of the captioned compoundas a colorless solid

Sources & evidence

ORD record
ord-f05932319e724ee79ac99bf1cddb4648
Source dataset
uspto-grants-1995_08
Patent number
US05446164

Reaction notes

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