3-Chloroaniline → tert-Butyl 4-(2-(3-chlorophenylamino)-2-oxoethyl)piperazine-1-carboxylate

HRID 416729Notes

Reaction equation

HRID 416729 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([OH:17])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=1)[NH2:22].C(N(C(C)C)CC)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>ClCCl>[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:15](=[O:17])[CH2:14][N:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)[CH:23]=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 79323-ChloroanilineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 27356422-{4-[(Tert-butoxy)carbonyl]piperazin-1-yl}acetic acid

Product 1

HCID 34196462tert-Butyl 4-(2-(3-chlorophenylamino)-2-oxoethyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round-bottomed flask containing 2-(1-tert-butoxycarbonyl-piperazin-4-yl)-acetic acid×2HCl (0.100 g, 0.36 mmol) was added 3-chloroaniline (0.050 g, 0.40 mmol) with the aid of anhydrous dichloromethane (4.5 ml). The reaction mixture was cooled into an ice-bath under argon, and then diisopropylethylamine (0.139 g, 1.08 mmol) was added followed by PyBOP (0.187 g, 0.36 mmol). The ice-bath was removed and the reaction mixture was allowed to stir for 20 h under argon. The solvent was removed in vacuo, the residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted with 25% ethyl acetate in dichloromethane. The title compound was obtained as a white solid (0.079 g, 62%). 1H-NMR (500 MHz, DMSO-d6) 1.40 (s, 9H, C(CH3)3), 2.46 (br s, 4H, piperazine N(CH2)2), 3.39 (br s, 4H, piperazine N(CH2)2), 3.16 (s, 2H, NCH2CO), 7.11 (d, J=8.59 Hz, 1H) and 7.55 (d, J=8.19 Hz, 1H) (4-ArH and 6-ArH), 7.34 (t, J=8.19 Hz, 1H, 5-ArH), 7.84 (t, J=1.9 Hz, 1H, 2-ArH), 9.89 (s, 1H, CONH);

Workup

  1. temperatureThe reaction mixture was cooled into an ice-bath under argon
  2. customThe ice-bath was removed
  3. customThe solvent was removed in vacuo
  4. customthe residue was absorbed on silica gel
  5. washwas eluted with 25% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-ca1922dd867b49a085887ad67d0f9e6a
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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