(2-Nitrophenyl)acetic acid → 3-isobutyl-5-(2-(2-nitrophenyl)acetyl)-3-phenyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-one

HRID 1747732Notes

Reaction equation

HRID 1747732 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]([OH:13])=O)([O-:3])=[O:2].[CH2:14]([C:18]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH2:23][NH:24][CH2:25][CH2:26][C:21]=2[C:20](=[O:27])[O:19]1)[CH:15]([CH3:17])[CH3:16].CCN(C(C)C)C(C)C.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[CH2:14]([C:18]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH2:23][N:24]([C:11](=[O:13])[CH2:10][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N+:1]([O-:3])=[O:2])[CH2:25][CH2:26][C:21]=2[C:20](=[O:27])[O:19]1)[CH:15]([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 77337(2-Nitrophenyl)acetic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 896147743-isobutyl-3-phenyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-one

Product 1

HCID 896284853-isobutyl-5-(2-(2-nitrophenyl)acetyl)-3-phenyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-oneYield 71.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(2-nitrophenyl)acetic acid (79 mg, 0.435 mmol), 3-isobutyl-3-phenyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-one (50 mg, 0.184 mmol), and N,N′-diisopropylethylamine (112 mg, 0.870 mmol) in THF (5 mL) was added BOP reagent (144 mg, 0.326 mmol) and the mixture was stirred at room temperature for 16 hours. The crude reaction mixture was concentrated to dryness and purified by column chromatography (12 g, SiO2, 0 to 100% ethyl acetate in hexanes) to provide 3-isobutyl-5-(2-(2-nitrophenyl)acetyl)-3-phenyl-4,5,6,7-tetrahydrofuro[3,4-c]pyridin-1(3H)-one (57 mg, 60%) as a white solid: 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 0.80-1.01 (m, 6H), 1.54-1.73 (m, 1H), 1.74-1.87 (m, 1H), 2.20-2.36 (m, 1H), 2.37-2.63 (m, 2H), 3.42-3.58 (m, 1H), 3.76-3.92 (m, 1H), 3.93-4.14 (m, 2H), 4.40 (m, 1H), 4.75 (d, J=19.59 Hz, 1H), 7.19-7.42 (m, 6H), 7.42-7.53 (m, 1H), 7.53-7.64 (m, 1H), 8.04-8.16 (m, 1H); MS m/z 435 (M+H)+, 457 (M+23)+, 433 (M−H)−.

Workup

  1. customThe crude reaction mixture
  2. concentrationwas concentrated to dryness
  3. custompurified by column chromatography (12 g, SiO2, 0 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-633a4f320de34b8cb7fad5fc117c3df5
Source dataset
uspto-grants-2015_10
Patent number
US09150582B2

Reaction notes

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