Sodium hydride → Ethyl 5-[(phenylmethyl)oxy]-1-(2,2,2-trifluoroethyl)-1H-indole-2-carboxylate

HRID 132811Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[CH:10][CH:9]=2)=[O:5])[CH3:2].[H-].[Na+].[F:25][C:26]([F:37])([F:36])[CH2:27]OS(C(F)(F)F)(=O)=O>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:27][C:26]([F:37])([F:36])[F:25])[C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 5-benzyloxyindole-2-carboxylic acid ethyl ester (purchased at Biosynth, ref B2000, 2.26 g, 1.0 eq.) in dimethylformamide (15 mL) was added to a suspension of sodium hydride (60% dispersion in oil, 367 mg, 1.2 eq.) in dimethylformamide. The reaction mixture was stirred 50 min at 70° C. 2,2,2-Trifluoroethyltrifluoromethanesulfonate (3.0 g, 1.7 eq.) was added and the reaction mixture was stirred overnight at 70° C. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic fractions were washed with water and brine, evaporated to dryness and purified on silica eluting with 9:1 cyclohexane/ethyl acetate to yield 1.9 g (66%) of the desired product as light yellow solid. MS (m/e): 378.5 (MH+, 100%).

Workup

stirringthe reaction mixture was stirred overnight at 70° C
customThe reaction mixture was partitioned between ethyl acetate and water
extractionThe aqueous layer was extracted with ethyl acetate
washthe combined organic fractions were washed with water and brine
customevaporated to dryness
custompurified on silica eluting with 9:1 cyclohexane/ethyl acetate

Sources & evidence

ORD record: ord-9cc5380f4fb548eab7ae16467c85b66b
Source dataset: uspto-grants-2008_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07388095B2

Reaction notes

Loading…