Acetic Acid → 2-(1-Benzyl-5-chloro-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide

HRID 1991583Notes

Reaction equation

HRID 1991583 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:18][C:19]([N:21]([CH3:23])[CH3:22])=[O:20])([OH:17])[C:9]1=[O:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:25]N1C(=O)CCC1=O.C(O)(=O)C.C1(C)C=CC=CC=1>O>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([Cl:25])=[CH:14][CH:15]=2)[C:10]([CH2:18][C:19]([N:21]([CH3:23])[CH3:22])=[O:20])([OH:17])[C:9]1=[O:24])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1140TolueneHCID 31398ChlorosuccinimideHCID 104039792-(1-Benzyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide

Product 1

HCID 100213452-(1-Benzyl-5-chloro-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamideYield 88.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A flask is charged with 2-(1-benzyl-3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-N,N-dimethyl-acetamide (Example 18) (10 g, 30.83 mmol), N-chloro succinimide (NCS) (4.12 g, 30.83 mmol), acetic acid (40 mL), and toluene (20 mL). The orange suspension is then stirred over night and becomes a homogeneous solution. After the addition of about 5 mL of water, the solvent is removed on the rotavapor. To the residue, water is added, and the product is extracted with chloroform. After drying and removal of solvent 11 g of crude product is obtained which after chromatography on silica (toluene:ethyl acetate 1:1) gives the title product (9.76 g, 88%) as yellow foam. 1H-NMR (CDCl3,300 MHz) δ 2.74, 3.08 (AB, 2H, 2J=16.3 Hz, CH2CONMe2); 4.85 (s, 2H, NCH2Ph); 6.32 (br s, 1H, OH); 6.58 (d, 1H, 3J=8.2 Hz, H-7); 7.10 (dd, 1H, 4J=2.0 Hz, H-6); 7.13-7.32 (m, 5H, Ph); 7.46 (d, 1H, H-4). 13C-NMR (CDCl3, 75 MHz) δ 35.77, 37.77 (N(CH3)2); 38.80 (CH2CONMe2); 44.27 (CH2Ph); 74.65 (C-3); 110.72 (C-7); 125.10 (C-4); 127.33 (Ph ortho-C); 127.90 (Ph para-C); 128.54 (C-5); 129.00 (Ph meta-C); 129.49 (C-6); 132.80 (C-9); 135.26 (C-15); 141.08 (C-8); 170.31 (C-11); 175.96 (C-2).

Workup

  1. customthe solvent is removed on the rotavapor
  2. additionTo the residue, water is added
  3. extractionthe product is extracted with chloroform
  4. customAfter drying
  5. customremoval of solvent 11 g of crude product
  6. customis obtained which after chromatography on silica (toluene:ethyl acetate 1:1)

Sources & evidence

ORD record
ord-848ae4a469f6459d870fec13bf8dbd20
Source dataset
uspto-grants-2010_01
Patent number
US07645886B2

Reaction notes

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