Diethyl Ether → 2-[3-(3,3-difluoro-2,2-dimethyl-indan-1-yl)-3H-imidazol-4-yl]-propan-2-ol

HRID 2089511Notes

Reaction equation

HRID 2089511 reaction equation
COC([C:5]1[N:6]([CH:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([F:20])([F:19])[C:11]2([CH3:22])[CH3:21])[CH:7]=[N:8][CH:9]=1)=O.[CH3:23][Mg]Br.C([O:28][CH2:29][CH3:30])C>C1COCC1>[F:20][C:12]1([F:19])[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]([N:6]2[C:5]([C:29]([OH:28])([CH3:30])[CH3:23])=[CH:9][N:8]=[CH:7]2)[C:11]1([CH3:22])[CH3:21]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 544461901-(2,2-Dimethyl-3,3-difluoro-indan-1-yl)-5-imidazolecarboxylic acid methyl esterHCID 178418573HCID 178418573, compound

Product 1

HCID 591993302-[3-(3,3-difluoro-2,2-dimethyl-indan-1-yl)-3H-imidazol-4-yl]-propan-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(3,3-difluoro-2,2-dimethyl-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester (300 mg, 0.98 mmol), which can be prepared as described in Example 18, in THF (10 mL) at 0° C. is added a 3.0 M solution of methylmagnesium bromide in diethyl ether (1.63 mL, 4.9 mmol). After one hour of stirring the reaction is quenched with saturated aqueous NH4Cl. The reaction is extracted three times with ethyl acetate and the organic extracts are combined, washed with brine, dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:5) to afford 2-[3-(3,3-difluoro-2,2-dimethyl-indan-1-yl)-3H-imidazol-4-yl]-propan-2-ol; HRMS: (ESI) m/z 307.1628 [(M+H)+: Calcd for C17H21N2OF2: 307.1622]; 1H NMR (400 MHz, CDCl3) δ ppm 0.97 (d, J=2.53 Hz, 3 H), 1.29 (d, J=3.28 Hz, 3 H), 1.79 (s, 6 H), 6.16 (d, J=3.79 Hz, 1 H), 6.89 (s, 1 H), 7.03 (s, 1 H), 7.33-7.41 (m, 1 H), 7.47-7.59 (m, 2 H), 7.62-7.72 (m, 1 H).

Workup

  1. customis quenched with saturated aqueous NH4Cl
  2. extractionThe reaction is extracted three times with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:5)

Sources & evidence

ORD record
ord-5519bf15088c4cf6808037d847c2c5b3
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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