Tetrahydrofuran → HCID 18431006, compound

HRID 1278584Notes

Reaction equation

HRID 1278584 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([C:11]2([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=3)[CH2:16][CH2:15][N:14]([CH2:17][CH:18]([CH3:22])[CH2:19][CH2:20][CH3:21])[CH2:13][CH2:12]2)=[N:9][CH:10]=1)=O.[CH2:31]([Mg]Br)[CH3:32].[CH2:35]1COC[CH2:36]1>C(OC)(C)(C)C>[CH3:30][O:29][C:25]1[CH:24]=[C:23]([C:11]2([C:8]3[N:9]=[CH:10][C:5]([C:3]([OH:2])([CH2:31][CH3:32])[CH2:35][CH3:36])=[CH:6][N:7]=3)[CH2:12][CH2:13][N:14]([CH2:17][CH:18]([CH3:22])[CH2:19][CH2:20][CH3:21])[CH2:15][CH2:16]2)[CH:28]=[CH:27][CH:26]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 70157931HCID 70157931, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 18431006HCID 18431006, compound

Reagents, catalysts & solvents 1

HCID 15413tert-Butyl methyl etherSolvent

Procedure

To a solution of 2-[4-(3-Methoxy-phenyl)-1-(2-methyl-pentyl)-piperidin-4-yl]-pyrimidine-5-carboxylic acid methyl ester (120 mg, 0.292 mmol) in THF (6 mL) at 0° C. was added ethyl magnesium bromide in t-butylmethyl ether (1 M, 3 mL). The reaction mixture was stirred at room temperature for 18 hours. The reaction was quenched by slow addition of water (5 mL). The aqueous layer was washed with CH2Cl2 (3×10 mL) and the organic extracts were dried (Na2SO4) and concentrated. Purification by flash chromatography with hexanes/EtOAc (3:1) yielded 28 mg of 3-{2-[4-(3-Methoxy-phenyl)-1-(2-methyl-pentyl)-piperidin-4-yl]-pyrimidin-5-yl}-pentan-3-ol. 1HNMR (400 MHz, CDCl3) δ 8.68 (s, 2H), 7.15 (t, 1H), 6.96-4.92 (comp, 2H), 6.67-6.64 (m, 1H), 3.73 (s, 3H), 2.94-2.90 (comp, 2H), 2.79-2.69 (comp, 2H), 2.35-2.28 (comp, 2H), 2.07-1.91 (comp, 3H), 1.81 (q, 2H), 1.62-1.59 (comp, 2H), 1.39-1.18 (comp, 4H), 0.89-0.82 (comp, 6H), 0.77 (t, 6H); MS (M+1) 440.3.

Workup

  1. customThe reaction was quenched by slow addition of water (5 mL)
  2. washThe aqueous layer was washed with CH2Cl2 (3×10 mL)
  3. dry with materialthe organic extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. customPurification by flash chromatography with hexanes/EtOAc (3:1)

Sources & evidence

ORD record
ord-ae064eab403346a38e12a34339991600
Source dataset
uspto-grants-2002_09
Patent number
US06444679B1

Reaction notes

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