Indomethacin → 2-tert-Butoxy-2-oxoethyl [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetate

HRID 1374070Notes

Reaction equation

HRID 1374070 reaction equation
[CH3:1][C:2]1[N:10]([C:11]([C:13]2[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=2)=[O:12])[C:9]2[CH:8]=[CH:7][C:6]([O:20][CH3:21])=[CH:5][C:4]=2[C:3]=1[CH2:22][C:23]([OH:25])=[O:24].C([O-])(O)=O.[Na+].[C:31]([O:35][C:36](=[O:39])[CH2:37]Br)([CH3:34])([CH3:33])[CH3:32]>CN(C=O)C>[Cl:19][C:16]1[CH:15]=[CH:14][C:13]([C:11]([N:10]2[C:9]3[C:4](=[CH:5][C:6]([O:20][CH3:21])=[CH:7][CH:8]=3)[C:3]([CH2:22][C:23]([O:25][CH2:37][C:36]([O:35][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:39])=[O:24])=[C:2]2[CH3:1])=[O:12])=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 3715IndomethacinHCID 79177tert-Butyl bromoacetateHCID 516892Sodium Bicarbonate

Product 1

HCID 133882022-tert-Butoxy-2-oxoethyl [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetateYield 99.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of indomethacin (6.388 g, 18 mmol) in anhydrous DMF (45 mL) were successively added NaHCO3 (1.4 g, 16.7 mmol) and tert-butylbromoacetate (2.95 g, 15 mmol) at room temperature under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2 days. The reaction mixture was then poured over ice-cold water, stirred, and the white solid obtained was filtered off, washed with water and dried. The product was recrystallized from EtOAc:hexane (1:4) to give the title compound (7.06 g, 88% yield) as a white soild. Mp 96–97° C. 1H NMR (300 MHz, CDCl3) δ 7.66 (d, J=8.5 Hz, 2H), 7.45 (d, J=8.5 Hz, 2H), 7.0 (d, J=2.4 Hz, 1H), 6.88 (d, J=9.0 Hz, 1H), 6.6 (dd, J=9.0 and 2.4 Hz, 1H), 4.52 (s, 2H), 3.83 (s, 3H), 3.77 (s, 2H), 2.37 (s, 3H), 1.44 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 170.1, 168.2, 166.6, 156.2, 139.2, 136.0, 133.8, 131.1 (2×C), 130.7, 130.5, 129.0 (2×C), 114.9, 112.1, 111.9, 101.1, 82.4, 61.5, 55.6, 29.7, 27.9, 13.4; LRMS (APIMS) m/z 472 (MH+).

Workup

  1. customat room temperature
  2. additionThe reaction mixture was then poured over ice-cold water
  3. stirringstirred
  4. customthe white solid obtained
  5. filtrationwas filtered off
  6. washwashed with water
  7. customdried
  8. customThe product was recrystallized from EtOAc:hexane (1:4)

Sources & evidence

ORD record
ord-652614dc1b2e40f996f2075fc5a33f8e
Source dataset
uspto-grants-2007_01
Patent number
US07163958B2

Reaction notes

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