Hydrochloric Acid → HCID 178442232, compound

HRID 216360Notes

Reaction equation

HRID 216360 reaction equation
Cl.[CH3:2][C:3]([CH3:50])([CH3:49])[CH2:4][C:5]1[N:6]=[C:7]([CH2:29][C:30]([C:36]2[CH:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][N:43]=3)=[CH:38][CH:37]=2)([OH:35])[C:31]([F:34])([F:33])[F:32])[N:8](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:9]=1>CO>[CH3:2][C:3]([CH3:50])([CH3:49])[CH2:4][C:5]1[N:6]=[C:7]([CH2:29][C:30]([C:36]2[CH:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][N:43]=3)=[CH:38][CH:37]=2)([OH:35])[C:31]([F:34])([F:33])[F:32])[NH:8][CH:9]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 68668056HCID 68668056, compound

Product 1

HCID 178442232HCID 178442232, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

Hydrogen chloride (4 M in 1,4-dioxane) (108 mL, 433 mmol) was added to an ambient temperature solution of 3-[4-(2,2-dimethylpropyl)-1-trityl-1H-imidazol-2-yl]-1,1,1-trifluoro-2-[4-(5-fluoropyridin-2-yl)phenyl]propan-2-ol (5.75 g, 8.7 mmol) in methanol (30 mL). After stirring at 70° C. for 1 h, volatiles were removed. The residue was partitioned between diethyl ether and 1N hydrochloric acid. The aqueous phase was washed with diethyl ether, basified with 2.5 N aqueous sodium hydroxide and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (sodium sulfate) and concentrated in vacuo to afford the title compound. LCMS: 422 (M+H). High pressure liquid chromatography (Chiralcel AD-H column) eluting with 15% isopropanol/heptane afforded the two individual enantiomers (E1 and E2). 1H NMR (500 MHz, CDCl3) δ 8.52 (s, 1H), 7.87 (d, J=7.3 Hz, 2H), 7.67-7.65 (m, 3H), 7.48-7.45 (m, 2H), 6.56 (s, 1H), 3.46 (dd, J=15.1, 51.1), 2.33 (s, 2H), 0.80 (s, 9H).

Workup

  1. customvolatiles were removed
  2. customThe residue was partitioned between diethyl ether and 1N hydrochloric acid
  3. washThe aqueous phase was washed with diethyl ether
  4. extractionextracted with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (sodium sulfate)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-020a89856150462d87ae082fc0c6b3a9
Source dataset
uspto-grants-2012_06
Patent number
US08193228B2

Reaction notes

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