Methyl iodide → Tert-butyl 4-(3-methoxy-4-(methoxycarbonyl)phenoxy)piperidine-1-carboxylate

HRID 1292034Notes

Reaction equation

HRID 1292034 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[C:17]([OH:25])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].I[CH3:27].[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[C:17]([O:25][CH3:27])[CH:16]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 105940774-(N-t-Butoxycarbonyl-4-piperidinyloxy)-2-hydroxybenzoic acid methyl ester

Product 1

HCID 10570851Tert-butyl 4-(3-methoxy-4-(methoxycarbonyl)phenoxy)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 4-(N-t-butoxycarbonyl-4-piperidinyloxy)-2-hydroxybenzoate (50 g, 0.14 mol) from Step 4 above and iodomethane (17.4 mL, 0.28 mol) in DMF (300 mL) at 0° C. was added NaH (6.55 g of a 60% suspension in mineral oil, 0.164 mol) in several portions over a period of 2 h. The resulting suspension was warmed to ambient temperature and stirred for 18 h. The mixture was quenched with methanol (5 mL) and concentrated under reduced pressure. The residue was suspended in EtOAc (500 mL) and washed with water (2×250 mL) and brine (250 mL). The EtOAc layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was purified by pressurized silica gel column chromatography using a gradient elution of 20-40% EtOAc-hexane. Methyl 4-(N-t-butoxycarbonyl-4-piperidinyloxy)-2-methoxybenzoate was obtained as a gum that solidified on standing (TLC: Rf = 0.25 (3:1 hexane:EtOAc); HPLC (method A) retention time= 9.72 min).

Workup

  1. customThe mixture was quenched with methanol (5 mL)
  2. concentrationconcentrated under reduced pressure
  3. washwashed with water (2×250 mL) and brine (250 mL)
  4. dry with materialThe EtOAc layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by pressurized silica gel column chromatography
  8. washa gradient elution of 20-40% EtOAc-hexane

Sources & evidence

ORD record
ord-2e1ab145331a48f7849e1fc1a3f5d9c2
Source dataset
uspto-grants-1998_05
Patent number
US05756497

Reaction notes

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