Phosphorus oxychloride → 5-fluoro-3-formyl-1-naphthalen-1-ylmethyl-1H-indole-2-carboxylic acid ethyl ester

HRID 642688Notes

Reaction equation

HRID 642688 reaction equation
O=P(Cl)(Cl)Cl.CN([CH:14]=[O:15])C1C=CC=CC=1.[CH2:16]([O:18][C:19]([C:21]1[N:22]([CH2:31][C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH:35]=[CH:34][CH:33]=2)[C:23]2[C:28]([CH:29]=1)=[CH:27][C:26]([F:30])=[CH:25][CH:24]=2)=[O:20])[CH3:17].C([O-])(=O)C.[Na+]>ClCCCl>[CH2:16]([O:18][C:19]([C:21]1[N:22]([CH2:31][C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH:35]=[CH:34][CH:33]=2)[C:23]2[C:28]([C:29]=1[CH:14]=[O:15])=[CH:27][C:26]([F:30])=[CH:25][CH:24]=2)=[O:20])[CH3:17]

Participants

6

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 66737N-MethylformanilideHCID 517045Sodium AcetateHCID 685783935-fluoro-1-naphthalen-1-ylmethyl-1H-indole-2-carboxylic acid ethyl ester

Product 1

HCID 866131895-fluoro-3-formyl-1-naphthalen-1-ylmethyl-1H-indole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
22 °C

Procedure

A mixture of POCl3 (0.79 ml) and N-methylformanilide (1.07 ml) was stirred at 22° C. for 10 min. To the solid formed was added a solution of 5-fluoro-1-naphthalen-1-ylmethyl-1H-indole-2-carboxylic acid ethyl ester (2.00 g from Example 15) in 1,2-dichloroethane (25 ml) and the solution was stirred at reflux temperature for 5 h. The solution was poured into a solution of ice-cold water (40 ml) containing sodium acetate (4.6 g) and stirring was continued at 22° for 2 h. The layers were separated, the aqueous layer extracted with dichloromethane, the combined extracts were dried, evaporated and the residue was chromatographed on silica using n-heptane/AcOEt (10:1) to give 5-fluoro-3-formyl-1-naphthalen-1-ylmethyl-1H-indole-2-carboxylic acid ethyl ester as a colorless solid. MS: 376.4 ([M+H]+).

Workup

  1. customTo the solid formed
  2. stirringthe solution was stirred
  3. temperatureat reflux temperature for 5 h
  4. stirringstirring
  5. waitwas continued at 22° for 2 h
  6. customThe layers were separated
  7. extractionthe aqueous layer extracted with dichloromethane
  8. customthe combined extracts were dried
  9. customevaporated
  10. customthe residue was chromatographed on silica

Sources & evidence

ORD record
ord-039b3d425b94433d934a50f53a1e0e18
Source dataset
uspto-grants-2010_04
Patent number
US07696240B2

Reaction notes

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