Chloride → HCID 19040912, compound

HRID 1683865Notes

Reaction equation

HRID 1683865 reaction equation
[Cl-].[F:2][C:3]([F:29])([F:28])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=2)([OH:17])[CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[CH:6][CH:5]=1.C(N(C(C)C)CC)(C)C.[CH2:39]([O:41][P:42]([C:47]1[CH:52]=[CH:51][C:50]([CH2:53]Cl)=[CH:49][CH:48]=1)([O:44][CH2:45][CH3:46])=[O:43])[CH3:40]>CS(C)=O.O>[CH2:45]([O:44][P:42]([C:47]1[CH:48]=[CH:49][C:50]([CH2:53][N:14]2[CH2:13][CH2:12][CH:11]([C:10]([C:7]3[CH:6]=[CH:5][C:4]([C:3]([F:2])([F:28])[F:29])=[CH:9][CH:8]=3)([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:25])[F:26])=[CH:20][CH:19]=3)[OH:17])[CH2:16][CH2:15]2)=[CH:51][CH:52]=1)([O:41][CH2:39][CH3:40])=[O:43])[CH3:46]

Participants

7

Reactant 4

HCID 312ChlorideHCID 81531DiisopropylethylamineHCID 15251776HCID 15251776, compoundHCID 19363748HCID 19363748, compound

Product 1

HCID 19040912HCID 19040912, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

To a stirred solution of 1.3 grams (0.004 mole) of 4-(diethylphosphono)phenylmethanol and two drops of pyridine in 10 mL of methylene chloride was added 0.39 mL (0.005 mole) of thionyl chloride. Upon completion of the addition, the reaction mixture was stirred for 30 minutes, then washed with 10 mL of water and 10 mL of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding the intermediate 4-(diethylphosphono)phenylmethyl chloride. The chloride was not further characterized. A solution of 2.7 grams (0.005 mole) of 4-[bis(4-trifluoromethylphenyl)hydroxymethyl]piperidine (prepared as in Step A of Example 17) in 10 mL of dimethyl sulfoxide was stirred, and 2.5 mL (excess) of diisopropylethylamine was added. To this was then added a solution of the methyl chloride, prepared above, in one mL of dimethyl sulfoxide. Upon completion of the addition, the reaction mixture was stirred at ambient temperature for one hour, then poured into water, and the mixture was extracted with one 150 mL portion of methylene chloride. The extract was washed with one 50 mL portion of an aqueous solution saturated with ammonium chloride and one 50 mL portion of water. The extract was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with pure ethyl acetate as the eluant. The product-containing fractions were combined and concentrated under reduced pressure, yielding 1.6 grams of N-[4-(diethylphosphono)phenylmethyl]-4-[bis(4-trifluoromethylphenyl)hydroxymethyl]piperidine. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of the addition
  2. extractionthe mixture was extracted with one 150 mL portion of methylene chloride
  3. washThe extract was washed with one 50 mL portion of an aqueous solution saturated with ammonium chloride and one 50 mL portion of water
  4. concentrationThe extract was concentrated under reduced pressure to a residue, which
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d0b6d06609a34bec8112ec37ad347934
Source dataset
uspto-grants-1997_06
Patent number
US05639763

Reaction notes

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