Ethyl isocyanate → HCID 68578198, compound

HRID 642702Notes

Reaction equation

HRID 642702 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)[C:8]2[C:13]([C:14]=1[CH2:15][OH:16])=[CH:12][C:11]([F:17])=[CH:10][CH:9]=2)=[O:5])[CH3:2].[CH2:29]([N:31]=[C:32]=[O:33])[CH3:30]>ClCCl.CN(C)C1C=CN=CC=1>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)[C:8]2[C:13]([C:14]=1[CH2:15][O:16][C:32](=[O:33])[NH:31][CH2:29][CH3:30])=[CH:12][C:11]([F:17])=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 8022Ethyl isocyanateHCID 68578168HCID 68578168, compound

Product 1

HCID 68578198HCID 68578198, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution 5-fluoro-3-hydroxymethyl-1-naphthalen-1-ylmethyl-1H-indole-2-carboxylic acid ethyl ester (51 mg, from Example 95) in dichloromethane (0.5 ml) was added 10 mg of ethyl isocyanate and stirring was continued at 22° C. for 16 h. 4-Dimethylaminopyridine (17 mg) was added and stirring was continued at 22° C. for 4 days. The mixture was chromatographed on silica using n-heptane/AcOEt (1:1) to give 3-ethylcarbamoyloxymethyl-5-fluoro-1-naphthalen-1-ylmethyl-1H-indole-2-carboxylic acid ethyl ester as a colorless solid. MS: 471.3 ([M+Na]+). The product was dissolved in EtOH (1 ml), diluted with 1N aqueous NaOH (0.187 ml) and the mixture was heated to 45° C. for 1 h. The mixture was acidified with AcOH and purified by HPLC (RP-18, CH3CH/H2O, gradient) to give 3-ethoxymethyl-5-fluoro-1-naphthalen-1-ylmethyl-1H-indole-2-carboxylic acid as a white solid. MS: 376.5 ([M−H]−).

Workup

  1. stirringstirring
  2. waitwas continued at 22° C. for 4 days
  3. customThe mixture was chromatographed on silica

Sources & evidence

ORD record
ord-c883da0e243945c2880e0dd4f1688190
Source dataset
uspto-grants-2010_04
Patent number
US07696240B2

Reaction notes

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