Triethylamine → (R)-4-[2-(6-Bromo-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475369Notes

Reaction equation

HRID 1475369 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][C@H:9]1[CH3:18])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:19][C:20]1[CH:28]=[C:27]2[C:23]([CH2:24][CH2:25][NH:26]2)=[CH:22][CH:21]=1.C(N(CC)CC)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]([N:26]2[C:27]3[C:23](=[CH:22][CH:21]=[C:20]([Br:19])[CH:28]=3)[CH2:24][CH2:25]2)=[O:17])[CH2:10][C@H:9]1[CH3:18])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733179PyBroPHCID 130983796-Bromo-2,3-dihydro-1H-indoleHCID 71003221HCID 71003221, compound

Product 1

HCID 71003222(R)-4-[2-(6-Bromo-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl esterYield 56.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-4-Carboxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (100 mg, 0.39 mmol), 6-bromo indoline (100 mg, 0.43 mmol) and triethylamine (0.148 mL, 1.06 mmol) were dissolved in DCM (1.94 mL) at ambient temperature. PyBrop (199 mg, 0.43 mmol) was added and the reaction stirred for 18 h. The solvent was removed in vacuo and the residue purified by column chromatography on silica gel (gradient elution, 0-100% EtOAc/petrol), to give the title compound (97 mg, 52%) as a pale yellow oil. 1H NMR (Me-d3-OD): 8.32 (1H, s), 7.24-7.10 (2H, m), 5.50 (1H, s), 4.38-4.17 (3H, m), 3.83 (1H, d), 3.31 (1H, s), 3.17 (2H, t), 2.91 (1H, d), 2.81 (1H, d), 2.33 (1H, dd), 2.20-2.09 (1H, m), 1.48 (9H, s), 1.30 (3H, d).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue purified by column chromatography on silica gel (gradient elution, 0-100% EtOAc/petrol)

Sources & evidence

ORD record
ord-987bc30c327c4a8d9f6122541c3375f0
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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