Formaldehyde → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-(3,3-dimethylmorpholino)-2-butynyl]piperazine

HRID 584207Notes

Reaction equation

HRID 584207 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]#[CH:16])[CH2:10][C@H:9]1[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[C:20]([CH3:25])[CH:19]=1)=[O:7].Cl.[CH3:36][C:37]1([CH3:43])[CH2:42][O:41][CH2:40][CH2:39][NH:38]1.C=O.[CH:46](N(C(C)C)CC)(C)C>O1CCOCC1.[Cu]I>[F:34][C:2]([F:1])([F:33])[C:3]1[CH:4]=[C:5]([CH:26]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:28]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]#[C:16][CH2:46][N:38]2[CH2:39][CH2:40][O:41][CH2:42][C:37]2([CH3:43])[CH3:36])[CH2:10][C@H:9]1[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[C:20]([CH3:25])[CH:19]=1)=[O:7]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 81531DiisopropylethylamineHCID 223428633,3-Dimethylmorpholine hydrochlorideHCID 53973560(2R)-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-propargylpiperazine

Product 1

HCID 54544444(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-(3,3-dimethylmorpholino)-2-butynyl]piperazine

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(2-propynyl)piperazine (0.49 g), 3,3-dimethylmorpholine hydrochloride (0.185 g), paraformaldehyde (62 mg), diisopropylethylamine (0.21 ml), and copper (1) iodide (20 mg) in 1,4-dioxane (5 ml) was stirred at 70° C. for 1.5 hours. After removal of the solvent by evaporation, the residue was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol (40:1). The fractions containing the objective compound was collected and evaporated under reduced pressure to give a syrup of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[4-(3,3-dimethylmorpholino)-2-butynyl]piperazine (0.45 g).

Workup

  1. customAfter removal of the solvent
  2. customby evaporation
  3. customthe residue was purified by column chromatography on silica gel using a mixed solvent of dichloromethane and methanol (40:1)
  4. additionThe fractions containing the objective compound
  5. customwas collected
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-6e2168cc59894a8d9dd299507199d71b
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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