Diisopropylethylamine → HCID 118207486, compound

HRID 1507193Notes

Reaction equation

HRID 1507193 reaction equation
Br[CH:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:3]1=[O:14].[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[CH:19][CH:18]=1.CCN(C(C)C)C(C)C>C(#N)C>[CH2:7]([N:4]1[CH2:5][CH2:6][CH:2]([N:26]2[CH2:27][CH2:28][CH:23]([C:20]3[CH:19]=[CH:18][C:17]([O:16][CH3:15])=[CH:22][CH:21]=3)[CH2:24][CH2:25]2)[C:3]1=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 106792704-(4-Methoxyphenyl)piperidineHCID 107295901-Benzyl-3-bromopyrrolidin-2-one2×

Product 1

HCID 118207486HCID 118207486, compoundYield 75.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 3-bromo-1-benzyl-pyrrolidin-2-one (1.4 g, 5.1 mmol)(intermediate 3), 4-(4-methoxyphenyl)-piperidine (0.98 g, 5.1 mmol) and DIPEA (3.6 mL, 20.6 mmol) in acetonitrile (15 mL) was heated at 90° C. for 18 h. The reaction mixture was concentrated and the residue was dissolved in ethyl acetate (150 mL), washed with water and brine, and dried over sodium sulfate. The organic layer was concentrated to yield 2.1 g of crude product, which was purified by flash chromatography on silica gel (24 g) using 100% EtOAc to yield 1-benzyl-3-(4-(4-methoxyphenyl)piperidin-1-yl)pyrrolidin-2-one (1.4 g, 71%). 1H NMR: 400 MHz, DMSO-d6: δ ppm 1.51-1.65 (m, 2H) 1.66-1.77 (m, 2H) 1.86-1.98 (m, 1H) 2.02-2.12 (m, 1H) 2.27-2.45 (m, 2H) 2.66-2.83 (m, 2H) 2.99-3.23 (m, 3H) 3.45-3.54 (m, 1H) 3.72 (s, 3H) 4.29-4.46 (m, 2H) 6.85 (d, J=9.04 Hz, 2H) 7.16 (d, J=9.04 Hz, 2H) 7.19-7.24 (m, 2H) 7.28 (s, 1H) 7.32-7.39 (m, 2H). LCMS: R.T. 1.76 min. LCMS (ES-API), 365.2 m/z (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in ethyl acetate (150 mL)
  3. washwashed with water and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationThe organic layer was concentrated
  6. customto yield 2.1 g of crude product, which
  7. customwas purified by flash chromatography on silica gel (24 g)

Sources & evidence

ORD record
ord-2c38e034fd8b4a0ea2073c3d576c91a2
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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