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Sodium Hydroxide → 2-(7-Fluoro-1H-indol-3-ylmethyl)-2-formylamino-malonic acid diethyl ester

HRID 401602
Notes
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Reaction equation

HRID 401602 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH2:11]N(C)C.[CH2:15]([O:17][C:18](=[O:28])[CH:19]([NH:25][CH:26]=[O:27])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH3:16].[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:23]([O:22][C:20](=[O:21])[C:19]([CH2:11][C:7]1[C:6]2[C:10](=[C:2]([F:1])[CH:3]=[CH:4][CH:5]=2)[NH:9][CH:8]=1)([NH:25][CH:26]=[O:27])[C:18]([O:17][CH2:15][CH3:16])=[O:28])[CH3:24]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 80617Diethyl formamidomalonateHCID 249051291-(7-Fluoro-1H-indol-3-yl)-N,N-dimethylmethanamine

Product 1

HCID 575633012-(7-Fluoro-1H-indol-3-ylmethyl)-2-formylamino-malonic acid diethyl esterYield 101.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A suspension of (7-fluoro-1H-indol-3-ylmethyl)-dimethyl-amine (550 mg, 0.0028 mol.), 2-formylamino-malonic acid diethyl ester (640 mg, 0.0031 mol.), and NaOH (30 mg) in toluene (20 mL) under argon was refluxed for 3 days. The reaction mixture was concentrated and purified by column chromatography on silica gel using 40% ethyl acetate-hexane to give 2-(7-Fluoro-1H-indol-3-ylmethyl)-2-formylamino-malonic acid diethyl ester (1.0 gm, 99%): mp 164-166° C., 1H NMR (500 MHz, CDCl3): 1.28 (t, J=7.5 Hz, 6H), 3.87 (s, 2H), 4.17-4.31 (m, 4H), 6.80 (s, 1H), 6.86-6.89 (dd, J=8.0 and 8.0 Hz, 1H), 6.97-7.01 (m, 2H), 7.27 (s, 1H), 8.18 (d, J=1.5 Hz, 1H), 8.27 (s, 1H).

Workup

  1. temperaturewas refluxed for 3 days
  2. concentrationThe reaction mixture was concentrated
  3. custompurified by column chromatography on silica gel using 40% ethyl acetate-hexane

Sources & evidence

ORD record
ord-44ebdc47458b4f898584fd9e2a46c9ac
Source dataset
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08741942B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes