Diisopropylethylamine → N-[4-(methylcarbonylamino)phenylmethyl]-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine

HRID 323821Notes

Reaction equation

HRID 323821 reaction equation
[F:1][C:2]([F:30])([F:29])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[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.[CH3:31][C:32]([NH:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41]Cl)=[CH:37][CH:36]=1)=[O:33].C(N(CC)C(C)C)(C)C>CS(C)=O>[CH3:31][C:32]([NH:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41][N:14]2[CH2:15][CH2:16][CH:11]([C:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:29])([F:1])[F:30])=[CH:9][CH:8]=3)([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:26])[F:27])=[CH:20][CH:19]=3)[OH:17])[CH2:12][CH2:13]2)=[CH:37][CH:36]=1)=[O:33]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 148705Acetamide, N-(4-(chloromethyl)phenyl)-HCID 190409264-[Bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine

Product 1

HCID 15515182N-[4-(methylcarbonylamino)phenylmethyl]-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidineYield 64.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a stirred solution of 0.4 gram (0.0008 mole) of 4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine in 10 mL of dimethyl sulfoxide was added a mixture of 0.2 gram (0.0008 mole) of 4-(methylcarbonylamino)phenylmethyl chloride and 0.6 mL (0.003 mole) of N,N-diisopropylethylamine. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 18 hours. After this time the reaction mixture was partitioned between an aqueous solution saturated with sodium bicarbonate and ethyl acetate. The organic layer was separated and washed with an aqueous solution saturated with sodium chloride. The organic layer was then concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with methylene chloride and mixtures of 10-50% acetone in methylene chloride as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding about 0.3 gram of N-[4-(methylcarbonylamino)phenylmethyl]-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of addition
  2. customAfter this time the reaction mixture was partitioned between an aqueous solution saturated with sodium bicarbonate and ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with an aqueous solution saturated with sodium chloride
  5. concentrationThe organic layer was then concentrated under reduced pressure to a residue, which
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-100d7b3015b748abae18239a38cdba7b
Source dataset
uspto-grants-2001_04
Patent number
US06214845B1

Reaction notes

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