Methyl iodide → (+/-)-3-(2,4-Dichloro-phenyl)-7-(1-methoxymethyl-butoxy)-2,6-dimethyl-pyrazolo[5,1-b]oxazole

HRID 1671300Notes

Reaction equation

HRID 1671300 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]2[N:17]=[C:16]([CH3:18])[C:15]([O:19][CH:20]([CH2:23][CH2:24][CH3:25])[CH2:21][OH:22])=[C:11]2[O:12][C:13]=1[CH3:14].[H-].[Na+].[CH3:28]I.[Cl-].[NH4+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]2[N:17]=[C:16]([CH3:18])[C:15]([O:19][CH:20]([CH2:21][O:22][CH3:28])[CH2:23][CH2:24][CH3:25])=[C:11]2[O:12][C:13]=1[CH3:14]

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 67212550(+/-)-2-[3-(2,4-Dichloro-phenyl)-2,6-dimethyl-pyrazolo[5,1-b]oxazol-7-yloxy]-pentan-1-ol

Product 1

HCID 59186038(+/-)-3-(2,4-Dichloro-phenyl)-7-(1-methoxymethyl-butoxy)-2,6-dimethyl-pyrazolo[5,1-b]oxazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of (±)-2-[3-(2,4-dichloro-phenyl)-2,6-dimethyl-pyrazolo[5,1-b]oxazol-7-yloxy]-pentan-1-ol (60 mg, 0.157 mmol) in THF (1.565 ml) at RT is added NaH (6.26 mg, 0.157 mmol). After 10 mins MeI (10.77 μl, 0.172 mmol) is added and the reaction mixture is stirred for a further 3 hours. An additional 1.leq of MeI (10.77 μl, 0.172 mmol) is added and reaction continued for 1 hour whereupon it is added to sat. ammonium chloride (50 ml) and the product extracted into EtOAc (60 ml). The organics are washed with brine, dried over MgSO4 and concentrated in vacuo. The crude reaction products are purified by ISCO combiflash chromatography, eluting with 0 to 100% (iso-hexane/EtOAc) on a 12 g SiO2-column to give (±)-3-(2,4-Dichloro-phenyl)-7-(1-methoxymethyl-butoxy)-2,6-dimethyl-pyrazolo[5,1-b]oxazole as a solid; MS: m/z 397.20 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 7.58 (2H, m), 7.41 (1H, dd), 4.03 (1H, m), 3.58 (2H, m), 3.44 (3H, s), 2.33 (3H, s), 2.30 (3H, s), 1.76 (2H, m), 1.57 (2H, m), 1.00 (3H, t).

Workup

  1. customreaction
  2. waitcontinued for 1 hour whereupon it
  3. extractionthe product extracted into EtOAc (60 ml)
  4. washThe organics are washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude reaction products
  8. customare purified by ISCO combiflash chromatography
  9. washeluting with 0 to 100% (iso-hexane/EtOAc) on a 12 g SiO2-column

Sources & evidence

ORD record
ord-a27e1914fe674b888828e3c0e9cdefcf
Source dataset
uspto-grants-2011_08
Patent number
US07994203B2

Reaction notes

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