Dimethylamine → 2-(4-Benzyloxy-5-fluoro-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide

HRID 1404074Notes

Reaction equation

HRID 1404074 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].[CH2:7]([O:14][C:15]1[C:23]([F:24])=[CH:22][CH:21]=[C:20]2[C:16]=1[CH:17]=[CH:18][NH:19]2)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH3:25][NH:26][CH3:27]>CCOCC.CCOC(C)=O>[CH2:7]([O:14][C:15]1[C:23]([F:24])=[CH:22][CH:21]=[C:20]2[C:16]=1[C:17]([C:1](=[O:5])[C:2]([N:26]([CH3:27])[CH3:25])=[O:3])=[CH:18][NH:19]2)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 3

HCID 674DimethylamineHCID 65578Oxalyl chlorideHCID 669271344-Benzyloxy-5-fluoro-1H-indole

Product 1

HCID 669271792-(4-Benzyloxy-5-fluoro-1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamideYield 87%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of oxalyl chloride (0.78 mL, 8.963 mmol) in anhydrous ether (20 mL) was added dropwise over 20 min to a 0° C. solution of 1-5a (1.44 g, 5.975 mmol) in anhydrous ether (20 mL). The reaction mixture was stirred at room temperature for 5 h, cooled to −20° C., and treated with a stream of dimethyl amine gas. The reaction was diluted with EtOAc, washed with water and brine, and dried over Na2SO4. After concentration, the resulting residue was recrystallized from EtOAc to provide the product (1-6a) as white crystals in 87% yield, 1.58 g. 1H NMR (300 MHz, CDCl3-d) δ (ppm) 2.92 (s, 3H), 2.94 (s, 3H), 5.17 (s, 2H), 6.91-7.00 (m, 2H), 7.29-7.37 (m, 3H), 7.58-7.61 (m, 2H), 7.70-7.72 (m, 1H), 10.02 (br, 1H). APCI [M+1]: 341.2.

Workup

  1. temperaturecooled to −20° C.
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationAfter concentration
  5. customthe resulting residue was recrystallized from EtOAc

Sources & evidence

ORD record
ord-0750015e655a45b78504c3c7ca5eab84
Source dataset
uspto-grants-2014_12
Patent number
US08912220B2

Reaction notes

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