Aluminium lithium hydride → [3-(2,2-Dimethyl-2,3-dihydro-benzofuran-3-yl)-3h-imidazol-4-yl]-methanol

HRID 2089512Notes

Reaction equation

HRID 2089512 reaction equation
C[O:2][C:3]([C:5]1[N:6]([CH:10]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[O:12][C:11]2([CH3:20])[CH3:19])[CH:7]=[N:8][CH:9]=1)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:19][C:11]1([CH3:20])[CH:10]([N:6]2[C:5]([CH2:3][OH:2])=[CH:9][N:8]=[CH:7]2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[O:12]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 675481143-(2,2-dimethyl-2,3-dihydro-benzofuran-3-yl)-3H-imidazole-4-carboxylic acid methyl ester

Product 1

HCID 59199401[3-(2,2-Dimethyl-2,3-dihydro-benzofuran-3-yl)-3h-imidazol-4-yl]-methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(2,2-dimethyl-2,3-dihydro-benzofuran-3-yl)-3H-imidazole-4-carboxylic acid methyl ester (2.2 g, 8.1 mmol), which can be prepared as described in Example 11, in THF (80 mL) at 0° C. is added LiAlH4 (310 mg, 8.1 mmol). After 30 minutes the reaction is quenched at 0° C. by the consecutive addition of 9:1 THF/H2O (3.5 mL), 2M aqueous NaOH (1.4 mL), and H2O (2.6 mL). The reaction is warmed to room temperature and diluted with THF (30 mL). After the addition of MgSO4 (3.75 g), the heterogeneous mixture is stirred for 15 min and then filtered through a pad of Celite®. The pad of Celite® is washed with ethyl acetate and the combined filtrate is concentrated. The resulting residue is purified by silica gel flash chromatography (methanol-dichloromethane, 0:1 to 1:20) to afford 3-(2,2-dimethyl-2,3-dihydro-benzofuran-3-yl)-3H-imidazol-4-yl]-methanol; HRMS: (ESI) m/z 245.1296 [(M+H)+: Calcd for C14H17N2O2: 245.1290]; 1H NMR (400 MHz, CDCl3) δ ppm 1.10 (s, 3 H), 1.54 (s, 3 H), 4.57-4.87 (m, 2 H), 5.60 (s, 1 H), 6.81-7.06 (m, 4 H), 7.22 (d, J=7.45 Hz, 1 H), 7.34 (t, J=7.45 Hz, 1 H).

Workup

  1. customAfter 30 minutes the reaction is quenched at 0° C. by the consecutive addition of 9:1 THF/H2O (3.5 mL), 2M aqueous NaOH (1.4 mL), and H2O (2.6 mL)
  2. additiondiluted with THF (30 mL)
  3. additionAfter the addition of MgSO4 (3.75 g)
  4. filtrationfiltered through a pad of Celite®
  5. washThe pad of Celite® is washed with ethyl acetate
  6. concentrationthe combined filtrate is concentrated
  7. customThe resulting residue is purified by silica gel flash chromatography (methanol-dichloromethane, 0:1 to 1:20)
  8. customto afford 3-(2,2-dimethyl-2,3-dihydro-benzofuran-3-yl)-3H-imidazol-4-yl]-methanol

Sources & evidence

ORD record
ord-76a9db5bf4e84bc1b9d595f61af515d7
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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