6-Benzyloxy-5-fluoro-1H-indole-2-carboxylic acid → 6-Benzyloxy-5-fluoro-1H-indole

HRID 1404080Notes

Reaction equation

HRID 1404080 reaction equation
[CH2:1]([O:8][C:9]1[CH:17]=[C:16]2[C:12]([CH:13]=[C:14](C(O)=O)[NH:15]2)=[CH:11][C:10]=1[F:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>CN1CCCC1=O.[Cu]>[CH2:1]([O:8][C:9]1[CH:17]=[C:16]2[C:12]([CH:13]=[CH:14][NH:15]2)=[CH:11][C:10]=1[F:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 583038746-Benzyloxy-5-fluoro-1H-indole-2-carboxylic acid

Product 1

HCID 583039226-Benzyloxy-5-fluoro-1H-indoleYield 60%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of compound 4-2 (2.58 g, 9.07 mmol) and copper (2.97 g, 45.1 mmol) in 80 mL of 1-methylpyrrolidin-2-one was heated at reflux overnight under nitrogen. After cooling to room temperature, the mixture was filtered through Celite and washed with EtOAc. The filtrate was partitioned between water and EtOAc (2×150 mL). The combined organic phase was washed with water and brine, and then dried over anhydrous Na2SO4. The black residue was purified by column chromatography (hexanes/EtOAc 2% to 12%) to give compound 4-3 (1.31 g, 60%) as a white solid. 1H NMR (CDCl3, 300 MHz) □ 5.16 (s, 2H), 6.94-6.98 (m, 1H), 6.96 (d, 1H, J=7.1), 7.10-7.14 (m, 1H), 7.29-7.42 (m, 4H), 7.44-7.50 (m, 2H), 8.01 (bs, 1H). APCI [M−1]: 240.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight under nitrogen
  3. filtrationthe mixture was filtered through Celite
  4. washwashed with EtOAc
  5. customThe filtrate was partitioned between water and EtOAc (2×150 mL)
  6. washThe combined organic phase was washed with water and brine
  7. dry with materialdried over anhydrous Na2SO4
  8. customThe black residue was purified by column chromatography (hexanes/EtOAc 2% to 12%)

Sources & evidence

ORD record
ord-b837f7bdda17476cb3f3a2991098f4c4
Source dataset
uspto-grants-2014_12
Patent number
US08912220B2

Reaction notes

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