2-Bromobenzoic acid → Tert-butyl 4-(2-bromobenzoyl)piperazine-1-carboxylate

HRID 1665584Notes

Reaction equation

C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[Br:20][C:21]1[CH:29]=[CH:28][CH:27]=[CH:26][C:22]=1[C:23]([OH:25])=O.CCN=C=NCCCN(C)C.Cl.[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1)=[O:48])([CH3:45])([CH3:44])[CH3:43]>CN(C=O)C.O>[C:42]([O:46][C:47]([N:49]1[CH2:54][CH2:53][N:52]([C:23](=[O:25])[C:22]2[CH:26]=[CH:27][CH:28]=[CH:29][C:21]=2[Br:20])[CH2:51][CH2:50]1)=[O:48])([CH3:45])([CH3:43])[CH3:44]

Participants

Conditions

Temperature: 10 °C

Procedure

HOBt (4 g, 29.6 mmol) and DIEA (8.7 g, 67.7 mmol) were added to a stirred solution of 2-bromo benzoic acid (5.6 g, 28.3 mmol) in DMF (50 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (7.76 g, 40.48 mmol) followed by piperazine-1-carboxylic acid tert-butyl ester (5 g, 26.9 mmol) were added. Then reaction mixture was stirred at the room temperature overnight. Water was added and the product was extracted with ethyl acetate. The ethyl acetate was washed with brine solution, dried over Na2SO4, and removed under reduced pressure to afford 9 g (90%) of 4-(2-bromo-benzoyl)-piperazine-1-carboxylic acid tert-butyl ester. 1H NMR: (DMSO-d6): δ 7.58 (d, 1H), 7.38 (t, 1H), 7.29 (d, 1H), 7.24 (d, 1H), 3.85 (m, 1H), 3.7 (m, 1H), 3.55 (t, 2H), 3.5 (m, 1H), 3.3 (m, 3H), 3.15 (m, 1H), 1.45 (s, 9H).

Workup

additionwere added
customThen reaction mixture
extractionthe product was extracted with ethyl acetate
washThe ethyl acetate was washed with brine solution
dry with materialdried over Na2SO4
customremoved under reduced pressure

Sources & evidence

ORD record: ord-334e494e16b343ddb98163ad28039856
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08039463B2

Reaction notes

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