Diethyl Ether → HCID 59205406, compound

HRID 2242355Notes

Reaction equation

HRID 2242355 reaction equation
[CH3:1][Mg]Br.C([O:6][CH2:7][CH3:8])C.C(OC[CH2:14][CH2:15][NH:16][C:17]([C:19]1[N:20]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]([F:40])([F:39])[F:38])[CH:31]=2)[C:21]2[C:26]([CH:27]=1)=[CH:25][C:24]([Cl:28])=[CH:23][CH:22]=2)=[O:18])(C)C>C1COCC1>[OH:6][C:7]([CH3:8])([CH3:1])[CH2:14][CH2:15][NH:16][C:17]([C:19]1[N:20]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]([F:38])([F:40])[F:39])[CH:31]=2)[C:21]2[C:26]([CH:27]=1)=[CH:25][C:24]([Cl:28])=[CH:23][CH:22]=2)=[O:18]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 59205405HCID 59205405, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 59205406HCID 59205406, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3.0M methyl magnesium bromide in diethyl ether (0.5 ml, 1.50 mmol) was added dropwise to a solution of 3-{[5-chloro-1-(3-trifluoromethoxybenzyl)-1H-indole-2-carbonyl]amino}propionic acid ethyl ester (Example 15) (200 mg, 0.42 mmol) in THF (4 ml) under nitrogen, maintaining temperature between 0 and 5° C. After stirring at 0° C. for 2 h, the reaction was quenched by slowly pouring the reaction mixture into water (2.0 ml). Volatile solvents were then removed under reduced pressure and the aqueous residue filtered. Purification was achieved by chromatography on silica using heptane:ethyl acetate (9:1 followed by 4:1) as eluent to afford 5-chloro-1-(3-trifluoromethoxybenzyl)-1H-indole-2-carboxylic acid (3-hydroxy-3-methylbutyl)amide as an off-white solid (28 mg, 15%).

Workup

  1. temperaturemaintaining temperature between 0 and 5° C
  2. customthe reaction was quenched
  3. additionby slowly pouring the reaction mixture into water (2.0 ml)
  4. customVolatile solvents were then removed under reduced pressure
  5. filtrationthe aqueous residue filtered
  6. customPurification

Sources & evidence

ORD record
ord-a9dc725a87ab4c359b605dfdeafb90c0
Source dataset
uspto-grants-2010_03
Patent number
US07671080B2

Reaction notes

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