1-Hydroxybenzotriazole → (+)-(3,5-Dimethylbenzoyl)-3-(3,4-dichlorophenyl)piperazine

HRID 443068Notes

Reaction equation

HRID 443068 reaction equation
C([NH:8]CC(O)=O)(OC(C)(C)C)=O.[CH3:13][C:14]1[CH:15]=[C:16]([CH:33]=[C:34]([CH3:36])[CH:35]=1)[C:17]([N:19]1[CH2:24][CH2:23][NH:22][CH:21]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=2)[CH2:20]1)=[O:18].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[NH3:8].[CH3:13][C:14]1[CH:15]=[C:16]([CH:33]=[C:34]([CH3:36])[CH:35]=1)[C:17]([N:19]1[CH2:24][CH2:23][NH:22][CH:21]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=2)[CH2:20]1)=[O:18]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 10292159(+)-(3,5-Dimethylbenzoyl)-3-(3,4-dichlorophenyl)piperazine

Product 2

HCID 222AmmoniaHCID 10292159(+)-(3,5-Dimethylbenzoyl)-3-(3,4-dichlorophenyl)piperazineYield 52.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of BOC glycine (0.918 g, 5.24 mmol), (+)-(3,5-dimethylbenzoyl)-3-(3,4-dichlorophenyl)piperazine (enantiomer B)(1.80 g, 4.95 mmol) (prepared in Example 19), DEC (0.983 g, 5.13 mmol), HOBT (0.687 g, 5.07 mmol) and Hunig's base (0.92 mL, 5.1 mmol) in CH2Cl2 (100 mL) was left stirring for 2.5 d. The reaction mixture was added to CH2Cl2 (200 mL) and washed with sat. NaHCO3 (3×100 mL), brine (100 mL), dried with MgSO4 and concentrated. The crude material was treated with MeOH saturated HCl (25 mL) for 10 h and concentrated. The resulting residue suspended in 0.3N NaOH (150 mL) and extracted with CH2Cl2, (3×50 mL). The combinded organic layers were washed with brine (50 mL), dried with MgSO4, concentrated, and purified by flash chromatography on silica gel, eluting with 20:1:0.2 CH2Cl2 /MeOH/conc. aq. NH3 to give 0.95 g of the titled product as a white solid. HRMS (FAB, M+H+); m/e calc'd [C31H24Cl2N3O2 ]+ : 420.1246 found 420.1254.

Workup

  1. washwashed with sat. NaHCO3 (3×100 mL), brine (100 mL)
  2. dry with materialdried with MgSO4
  3. concentrationconcentrated
  4. additionThe crude material was treated with MeOH saturated HCl (25 mL) for 10 h
  5. concentrationconcentrated
  6. extractionextracted with CH2Cl2, (3×50 mL)
  7. washThe combinded organic layers were washed with brine (50 mL)
  8. dry with materialdried with MgSO4
  9. concentrationconcentrated
  10. custompurified by flash chromatography on silica gel
  11. washeluting with 20:1:0.2 CH2Cl2 /MeOH/conc

Sources & evidence

ORD record
ord-1c0eabae8ff34908b8963cf8e479fea3
Source dataset
uspto-grants-1999_04
Patent number
US05892039

Reaction notes

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