Isobutyraldehyde → tert-Butyl [2-(2-hydroxy-3-methylbutyl)-5-methoxyphenyl]carbamate

HRID 2409988Notes

Reaction equation

HRID 2409988 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:17])=[C:7]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:8]=1.C([Li])(CC)C.[CH3:23][CH:24]([CH3:27])[CH:25]=[O:26].[Cl-].[NH4+]>O1CCCC1>[OH:26][CH:25]([CH:24]([CH3:27])[CH3:23])[CH2:17][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][C:7]=1[NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:14])[CH3:15]

Participants

6

Reactant 4

HCID 6561IsobutyraldehydeHCID 25517Ammonium ChlorideHCID 10609920tert-Butyl (5-methoxy-2-methylphenyl)carbamateHCID 178418400CID 53628100

Product 1

HCID 86703306tert-Butyl [2-(2-hydroxy-3-methylbutyl)-5-methoxyphenyl]carbamateYield 50.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under an argon atmosphere, to a solution of tert-butyl (5-methoxy-2-methylphenyl)carbamate (1.42 g) in tetrahydrofuran (30 mL) was slowly added dropwise sec-butyllithium (1.06 mol/L hexane-cyclohexane solution, 12.5 mL) at −40° C., and the mixture was stirred for 15 minutes. Then, a solution of 2-methylpropionaldehyde (476 mg) in tetrahydrofuran (3 mL) was added dropwise thereto, and the mixture was stirred at −40° C. for 15 minutes, and then stirred at room temperature for additional 40 minutes. To the reaction mixture was added a saturated aqueous ammonium chloride solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (929 mg). 1H-NMR (CDCl3) δ ppm: 0.96-1.06 (6H, m), 1.52 (9H, s), 1.70-1.83 (1H, m), 1.90 (1H, d, J=3.8 Hz), 2.57-2.75 (2H, m), 3.48-3.59 (1H, m), 3.80 (3H, s), 6.59 (1H, dd, J=2.8, 8.5 Hz), 7.00 (1H, d, J=8.5 Hz), 7.43 (1H, br s), 7.91 (1H, br s).

Workup

  1. stirringthe mixture was stirred at −40° C. for 15 minutes
  2. stirringstirred at room temperature for additional 40 minutes
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-f24118c35c3b48849763169d45edba57
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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