Ammonium Chloride → 1-[2-Methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-yl]-2-phenyl-ethanone

HRID 346846Notes

Reaction equation

HRID 346846 reaction equation
[CH3:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:11]([O:20][Si:21]([CH2:26][CH3:27])([CH2:24][CH3:25])[CH2:22][CH3:23])([C:16]([F:19])([F:18])[F:17])[C:12]([F:15])([F:14])[F:13])[CH:8]=2)[NH:3]1.CCN(C(C)C)C(C)C.[C:37]1([CH2:43][C:44](Br)=[O:45])[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.[NH4+].[Cl-]>C(Cl)Cl.CCOCC>[CH3:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:11]([O:20][Si:21]([CH2:24][CH3:25])([CH2:22][CH3:23])[CH2:26][CH3:27])([C:12]([F:15])([F:14])[F:13])[C:16]([F:17])([F:18])[F:19])[CH:8]=2)[N:3]1[C:44](=[O:45])[CH2:43][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 89742Benzeneacetyl bromideHCID 210822122-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole

Product 1

HCID 210821961-[2-Methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-yl]-2-phenyl-ethanoneYield 94.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 101 mg (0.24 mmol) of 2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole (example 51.2) in CH2Cl2 was treated with 0.05 mL (0.3 mmol) of DIPEA and then with 0.03 mL (0.24 mmol) of phenylacetylbromide at 0° C. The mixture was stirred at RT for 3 hrs and then distributed between Et2O a saturated aqueous solution of NH4Cl. The combined organic phases were dried over Na2SO4 and evaporated to yield 120 mg of 1-[2-methyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-indol-1-yl]-2-phenyl-ethanone. This crude was dissolved in 2 mL of THF and treated with 0.9 mL of a 1M BH3 soution in THF. After stirring for 10 hrs at RT the mixture was distributed between Et2O and a saturated aqueous solution of NH4Cl. The combined organic phases were dried over Na2SO4 and evaporated to yield 135 mg of 2-methyl-1-phenethyl-5-(2,2,2-trifluoro-1-triethylsilanyloxy-1-trifluoromethyl-ethyl)-2,3-dihydro-1H-indole, of which 30 mg were dissolved in 1 mL of THF and treated with 0.07 mL of 1M TBAF in THF. Stirring for 30 min, evaporation, and column chromatography on silica gel with n-heptane/EtOAc (4:1) yielded 12 mg (51%) of 1,1,1,3,3,3-hexafluoro-2-(2-methyl-1-phenethyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol, colorless waxy solid, MS: 404 (MH+).

Workup

  1. customat 0° C
  2. dry with materialThe combined organic phases were dried over Na2SO4
  3. customevaporated

Sources & evidence

ORD record
ord-45c7ba17cd8348c1849c7e0cf7818d92
Source dataset
uspto-grants-2007_02
Patent number
US07173048B2

Reaction notes

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