Acetic Acid → 1-(4-chlorobenzoyl)-5-methoxy-1H-indole-3-acetic acid

HRID 527446Notes

Reaction equation

HRID 527446 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10]([CH2:19][C:20]([O:22]C)=[O:21])=[CH:9]2)=[O:7])=[CH:4][CH:3]=1.[OH-].C[Sn+](C)C.ClCCl.CC(O)=O>ClCCCl>[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10]([CH2:19][C:20]([OH:22])=[O:21])=[CH:9]2)=[O:7])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 11217597Stannane, hydroxytrimethyl-HCID 57563309methyl 2-(1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl)acetate

Product 1

HCID 47116971-(4-chlorobenzoyl)-5-methoxy-1H-indole-3-acetic acid

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
130 °C

Procedure

In a microwave process vial methyl 2-(1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl)acetate (10 mg, 0.028 mmol) was dissolved in 1,2-dichloro ethane (1 mL) and after addition of trimethyltin hydroxide (25 mg, 0.14 mmol) the reaction mixture was heated for 30 min at 130° C. in a microwave (TLC analysis indicated complete reaction). Dichloromethane (1 mL) and 50% AcOH (2 mL) were added to the cold reaction solution and the resulting biphasic mixture was agitated until both layers were clear. The organic phase was collected, washed with brine, dried over Na2SO4 and filtered (using a phase separator syringe with drying cartridge). Removal of the solvent (dichloromethane) in vacuo and following silica gel chromatography using an ethyl acetate/hexane gradient (0.5% AcOH) afforded the pure title compound quantitatively. C18H14ClNO4, Mr=343.76; 1H NMR (400 MHz, DMSO-d6) d: 3.67 (s, 2H), 3.81 (s, 3H), 6.99 (dd, J=2.4/9.2 Hz, 1H), 7.12 (d, J=2.4 Hz, 1H), 7.32 (s, 1H), 7.65-7.77 (m, 4H), 8.17 (d, J=9.2 Hz, 1H); LCMS (ESI) tR: 2.60 min (>99%, ELSD), m/z: 344.0 [M+1]+.

Workup

  1. customThe organic phase was collected
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. custom(using a phase separator syringe with drying cartridge)
  6. customRemoval of the solvent (dichloromethane) in vacuo

Sources & evidence

ORD record
ord-5c85583a7ce343d29bcfa66610b1b22b
Source dataset
uspto-grants-2016_05
Patent number
US09346803B2

Reaction notes

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