Tetrahydrofuran → 4-[2-(2,6-Diethylphenyl)-4-methoxy-6-methylpyrimidin-5-yl]heptan-4-ol

HRID 1091948Notes

Reaction equation

HRID 1091948 reaction equation
C[O:2][C:3]([C:5]1[C:6]([O:22][CH3:23])=[N:7][C:8]([C:12]2[C:17]([CH2:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:20][CH3:21])=[N:9][C:10]=1[CH3:11])=O.[CH2:24]([Mg]Cl)[CH2:25][CH3:26].[CH2:29]1[CH2:33][O:32][CH2:31][CH2:30]1>>[CH2:20]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]([CH2:18][CH3:19])[C:12]=1[C:8]1[N:7]=[C:6]([O:22][CH3:23])[C:5]([C:3]([OH:2])([CH2:30][CH2:29][CH3:33])[CH2:24][CH2:25][CH3:26])=[C:10]([CH3:11])[N:9]=1)[CH3:21].[CH2:20]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]([CH2:18][CH3:19])[C:12]=1[C:8]1[N:7]=[C:6]([O:22][CH3:23])[C:5]([CH:31]([OH:32])[CH2:30][CH2:29][CH3:33])=[C:10]([CH3:11])[N:9]=1)[CH3:21]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 575315802-(2,6-Diethyl-phenyl)-4-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl esterHCID 178455855HCID 178455855, compound

Product 2

HCID 575314274-[2-(2,6-Diethylphenyl)-4-methoxy-6-methylpyrimidin-5-yl]heptan-4-olHCID 665896771-[2-(2,6-Diethylphenyl)-4-methoxy-6-methylpyrimidin-5-yl]butan-1-ol

Procedure

To a solution of 2-(2,6-diethyl-phenyl)-4-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester (3.3 g, 0.01 mol) at 0° C. in dry THF (50 mL) under nitrogen with magnetic stirring is added n-propyl magnesium chloride (26 mL, 2.0 M, 0.05 mol) in dropwise fashion. The reaction mixture is allowed to warm to room temperature and stirred for 2 h. The reaction mixture is quenched with a saturated aqueous NH4Cl solution (20 mL) and extracted with DCM (100 mL). The DCM layer is dried over sodium sulfate, filtered and evaporated to obtain a residue. Purification by chromatography over silica gel eluting with 10% EtOAc-hexanes affords the title compound as a colorless oil and 1-[2-(2,6-diethylphenyl)-4-methoxy-6-methylpyrimidin-5-yl]butan-1-ol as a colorless oil. Title compound 1H NMR (300 MHz, CDCl3): δ 7.23-7.29 (m, 1H), 7.13 (d, J=9 Hz, 2H), 3.95 (s, 3H), 2.72 (s, 3H), 2.41 (q, J=7.5 Hz, 4H), 2.18-2.30 (m, 2H), 1.66-1.81 (m, 2H), 1.42-1.54 (m, 2H), 1.05-1.18 (m, 8H), 0.91 (t, J=7.2 Hz, 6H); LC-MS found 371 (MH+). 1-[2-(2,6-Diethylphenyl)-4-methoxy-6-methylpyrimidin-5-yl]butan-1-ol NMR (300 MHz, CDCl3): δ 7.23-7.28 (m, 1H), 7.1 (d, J=9 Hz, 2H), 4.81-5.11 (m, 1H), 4.01(s, 3H), 2.45 (s, 3H), 2.55 (q, J=7.5 Hz, 4H), 1.88-2.00 (m, 1H), 1.30-1.81 (m, 4H), 1.10 (q, J=7.8, 4.8 Hz, 6H), 0.91 (t, J=7.2 Hz, 6H); LC-MS found 328 (MH+).

Workup

  1. customThe reaction mixture is quenched with a saturated aqueous NH4Cl solution (20 mL)
  2. extractionextracted with DCM (100 mL)
  3. dry with materialThe DCM layer is dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customto obtain a residue
  7. customPurification by chromatography over silica gel eluting with 10% EtOAc-hexanes

Sources & evidence

ORD record
ord-10b2774f41bd49a2b33ede40bed5efc0
Source dataset
uspto-grants-2012_03
Patent number
US08129395B2

Reaction notes

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