Diisopropylethylamine → tert-butyl 3-(2-neopentyl-1-(2-(trifluoromethoxy)ethyl)-1H-benzo[d]imidazol-5-ylthio)azetidine-1-carboxylate

HRID 241644Notes

Reaction equation

HRID 241644 reaction equation
Br[C:2]1[CH:22]=[CH:21][C:5]2[N:6]([CH2:14][CH2:15][O:16][C:17]([F:20])([F:19])[F:18])[C:7]([CH2:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[N:8][C:4]=2[CH:3]=1.[SH:23][CH:24]1[CH2:27][N:26]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:25]1.C(N(CC)C(C)C)(C)C>O1CCOCC1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:9]([C:7]1[N:6]([CH2:14][CH2:15][O:16][C:17]([F:20])([F:19])[F:18])[C:5]2[CH:21]=[CH:22][C:2]([S:23][CH:24]3[CH2:25][N:26]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:27]3)=[CH:3][C:4]=2[N:8]=1)[C:10]([CH3:13])([CH3:12])[CH3:11]

Participants

8

Reactant 3

HCID 81531DiisopropylethylamineHCID 58513580tert-Butyl 3-sulfanylazetidine-1-carboxylateHCID 585135965-bromo-2-neopentyl-1-(2-(trifluoromethoxy)ethyl)-1H-benzo[d]imidazole

Product 1

HCID 58513590tert-butyl 3-(2-neopentyl-1-(2-(trifluoromethoxy)ethyl)-1H-benzo[d]imidazol-5-ylthio)azetidine-1-carboxylateYield 81.5%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 5-bromo-2-neopentyl-1-(2-(trifluoromethoxy)ethyl)-1H-benzo[d]imidazole (STEP A, 265 mg, 0.700 mmol), tert-butyl 3-mercaptoazetidine-1-carboxylate (STEP D of Example 1, 189 mg, 0.999 mmol), Xantphos (20.2 mg, 0.0350 mmol), tris(dibenzylideneacetone)dipalladium (16.0 mg, 0.0175 mmol) and N,N-diisopropylethylamine (245 microL, 1.40 mmol) in 1,4-dioxane (4 mL) was stirred at 160° C. for 1 h under microwave. The mixture was diluted with ethyl acetate and filtered through a celite. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (hexane-ethyl acetate, gradient) to give the title compound (278 mg, 81%).

Workup

  1. filtrationfiltered through a celite
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue was purified by silica gel column chromatography (hexane-ethyl acetate, gradient)

Sources & evidence

ORD record
ord-551daae415654aa68146d63cf51636aa
Source dataset
uspto-grants-2014_02
Patent number
US08653063B2

Reaction notes

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