Trimethylsilyldiazomethane → methyl 6-fluoro-5-methyl-1H-indole-2-carboxylate

HRID 1098656Notes

Reaction equation

HRID 1098656 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([OH:13])=[O:12])[NH:8]2)=[CH:4][C:3]=1[CH3:14].[Si](C=[N+]=[N-])(C)(C)[CH3:16]>CO.C1(C)C=CC=CC=1>[CH3:16][O:12][C:11]([C:7]1[NH:8][C:9]2[C:5]([CH:6]=1)=[CH:4][C:3]([CH3:14])=[C:2]([F:1])[CH:10]=2)=[O:13]

Participants

4

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 534029636-Fluoro-5-methyl-1H-indole-2-carboxylic acid

Product 1

HCID 58132923methyl 6-fluoro-5-methyl-1H-indole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 21867641Toluene methanolSolvent

Procedure

To a cooled solution of 6-Fluoro-5-Methyl-1H-indole-2-carboxylic acid in MeOH/toluene (1C) (200 mL, 1:1) was added TMS-diazomethane (2.0 M solution in diethylether, 1.05 eq.) dropwise and the reaction was allowed to warm up to room temperature over 1 h. The reaction mixture was concentrated and purified using triturating with CH2Cl2 and hexane and collecting the solids by filtration to obtain 6-Fluoro-5-Methyl-1H-indole-2-carboxylic acid methyl ester 1D (3.5 g). The concentrated filtrate was purified using chromatography over SiO2 using 0 to 40% ethyl acetate in hexanes to provide an additional amount of 6-Fluoro-5-Methyl-1H-indole-2-carboxylic acid methyl ester 1D (1.0 g). Overall yield (60%). 1H NMR (400 MHz, d6-DMSO): 2.26 (s, 3H), 3.83 (s, 3H), 7.07 (s, 1H), 7.08 (d, J=10.2 Hz, 1H), 7.49 (d, J=8.1 Hz, 1H), 11.9 (s, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified
  3. customusing triturating with CH2Cl2 and hexane
  4. customcollecting the solids
  5. filtrationby filtration

Sources & evidence

ORD record
ord-d0f6e057c7b1436c86ed7fb4acc78183
Source dataset
uspto-grants-2012_03
Patent number
US08143305B2

Reaction notes

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