Boron tribromide → HCID 86279750, compound

HRID 588834Notes

Reaction equation

HRID 588834 reaction equation
[C:1]([N:5]1[CH2:8][CH:7]([N:9]2[CH2:14][CH2:13][CH:12]([C:15]([NH:17][CH2:18][C:19]3[CH:24]=[C:23]([Cl:25])[C:22]([Cl:26])=[CH:21][C:20]=3[O:27]C)=[O:16])[CH2:11][CH2:10]2)[CH2:6]1)(=[O:4])[CH:2]=[CH2:3].B(Br)(Br)Br.C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:26][C:22]1[C:23]([Cl:25])=[CH:24][C:19]([CH2:18][NH:17][C:15]([CH:12]2[CH2:11][CH2:10][N:9]([CH:7]3[CH2:8][N:5]([C:1](=[O:4])[CH:2]=[CH2:3])[CH2:6]3)[CH2:14][CH2:13]2)=[O:16])=[C:20]([OH:27])[CH:21]=1

Participants

5

Reactant 3

HCID 25134Boron tribromideHCID 516892Sodium BicarbonateHCID 90460107HCID 90460107, compound

Product 1

HCID 86279750HCID 86279750, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(1-acryloylazetidin-3-yl)-N-(4,5-dichloro-2-methoxybenzyl)piperidine-4-carboxamide (150 mg, 0.35 mmol) in DCM (15 mL) at −60° C., BBr3 (0.6 g, 2.4 mmol) was added dropwise. The resulting mixture was allowed to warm to room temperature and stirred for 1 h. The mixture was poured into ice-water, basified with saturated NaHCO3 solution to adjust the pH to 8-9, and then extracted with DCM. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=20:1) to afford the desired product (34 mg, 24% yield). 1H NMR (400 MHz, DMSO-d6) δ: 10.34 (s, 1H), 8.2-8.25 (m, 1H), 7.2 (s, 1H), 7.0 (s, 1H), 6.91 (s, 1H), 6.33-6.27 (m, 1H), 6.12-6.07 (dd, J=2.4, 12.4 Hz, 1H), 5.68-5.65 (dd, J=2.4, 10.4 Hz, 1H), 4.24-4.20 (m, 1H), 4.17-4.14 (m, 2H), 4.14-3.99 (m, 1H), 3.94-3.90 (m, 1H), 3.73-3.70 (m, 1H), 3.10 (s, 1H), 2.84-2.80 (m, 2H), 2.22 (m, 1H), 1.80 (s, 2H), 1.73-1.71 (m, 2H), 1.63-1.57 (m, 2H). ESI-MS m/z: 412.2[M+H]+.

Workup

  1. extractionextracted with DCM
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-706d6021a5f84203aecfef0e28712566
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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