Triethylamine → (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl4-(4-fluorobenzyl)-5-((hydroxy)methyl)piperazine

HRID 488390Notes

Reaction equation

HRID 488390 reaction equation
[F:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][N:7]2[CH2:12][C@H:11]([CH3:13])[NH:10][CH2:9][C@@H:8]2[CH2:14][OH:15])=[CH:4][CH:3]=1.C(N(CC)CC)C.[Cl:25][C:26]1[CH:36]=[CH:35][C:29]([O:30][CH2:31][C:32](Cl)=[O:33])=[CH:28][CH:27]=1>C(Cl)Cl>[Cl:25][C:26]1[CH:36]=[CH:35][C:29]([O:30][CH2:31][C:32]([N:10]2[CH2:9][C@H:8]([CH2:14][OH:15])[N:7]([CH2:6][C:5]3[CH:16]=[CH:17][C:2]([F:1])=[CH:3][CH:4]=3)[CH2:12][C@H:11]2[CH3:13])=[O:33])=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 77771p-Chlorophenoxyacetyl chlorideHCID 57226061(2R,5S)-1-(4-fluorobenzyl)-2-(hydroxy)methyl-5-methylpiperazine

Product 1

HCID 11441144(2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl4-(4-fluorobenzyl)-5-((hydroxy)methyl)piperazineYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (2R,5S)-1-(4-fluorobenzyl)-2-(hydroxy)methyl-5-methylpiperazine (1.6 g, 6.7 mmol) in CH2Cl2 (30 mL) was added triethylamine (excess) and 4-chlorophenoxyacetyl chloride (1.5 g, 7.4 mmol, dropwise in 10 mL solution of CH2Cl2). The resultant mixture was stirred at ambient temperature. After 20 minutes, analysis by analytical TLC showed complete consumption of starting material had occurred. The mixture was concentrated of volatiles in vacuo and the residue taken up in CH2Cl2. This was washed with saturated aqueous NaHCO3 solution, then water, then brine, dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash column chromatography on silica gel afforded 2.16 g (79% yield) of (2R,5R)-1-((4-chlorophenoxy)methyl)carbonyl-2-methyl-4-(4-fluorobenzyl)-5-((hydroxy)methyl)piperazine, as a solid yellow foam: NMR (DMSO-d6) 7.7 (br s, 2), 7.3 (m, 4), 6.9 (d, 2), 5.0-4.2 (m, 5), 4.0-3.2 (m, 7), 1.2 (m, 3) ppm; MS (LSIMS) 406.

Workup

  1. customconsumption of starting material
  2. concentrationThe mixture was concentrated of volatiles in vacuo
  3. washThis was washed with saturated aqueous NaHCO3 solution
  4. dry with materialwater, then brine, dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-aef5f97a97224375922ba1f6334c0001
Source dataset
uspto-grants-2005_12
Patent number
US06972290B2

Reaction notes

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