Water → Methyl 3-amino-5-(tert-butyl)furan-2-carboxylate

HRID 1698904Notes

Reaction equation

HRID 1698904 reaction equation
[H-].[Na+].[C:3]([O:7][CH3:8])(=[O:6])[CH2:4][OH:5].Cl[C:10]([C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:11][C:12]#[N:13].O>COCCOC>[NH2:13][C:12]1[CH:11]=[C:10]([C:14]([CH3:17])([CH3:16])[CH3:15])[O:5][C:4]=1[C:3]([O:7][CH3:8])=[O:6]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 66774Methyl GlycolateHCID 27356613-Chloro-4,4-dimethylpent-2-enenitrile

Product 1

HCID 18322376Methyl 3-amino-5-(tert-butyl)furan-2-carboxylateYield 17%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
85 °C

Procedure

To a slurry of NaH (5.98 g, 0.24 mol, 2.6 equiv) in anh. DME (800 mL) at 0° C. was added methyl glycolate (23.0 g, 0.26 mol, 2.8 equiv) over 20 min. The mixture was stirred for 1 h at room temp. and a solution of 3-chloro-4,4-dimethyl-2-pentenenitrile (13.1 g, 0.091 mol) in DME (100 mL) was added. The resulting solution was heated to 85° C. for 42 h, cooled to room temp., and treated with H2O (100 mL). The resulting mixture was separated between H2O (200 mL) and EtOAc (300 mL). The aqueous layer was extracted with EtOAc (2×200 mL). The combined organic layers were washed with a saturated NaCl solution, dried (Na2SO4), and concentrated under reduced pressure. The residual oil was purified by flash chromatography (300 g SiO2, gradient from 50% CH2Cl2/hexane to 20% EtOAc/CH2Cl2) to give methyl 3-amino-5-tert-butylfuran-2-carboxylate as a yellow solid (2.98 g, 17%): mp 91-2° C.; TLC (20% EtOAc/hexane) Rf0.36; 1H NMR (CDCl3) δ1.26 (s, 9H), 3.84 (s, 3H), 4.54 (br s, 2H), 5.75 (s, 1H); 13C NMR (CDCl3) δ28.5 (3C), 33.0, 50.7, 98.5, 128.8, 131.0, 160.7, 168.3.

Workup

  1. temperaturecooled to room temp.
  2. customThe resulting mixture was separated between H2O (200 mL) and EtOAc (300 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×200 mL)
  4. washThe combined organic layers were washed with a saturated NaCl solution
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe residual oil was purified by flash chromatography (300 g SiO2, gradient from 50% CH2Cl2/hexane to 20% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-fdb5fa4e85f240eabd47c3cd7c8dbcf5
Source dataset
uspto-grants-2002_02
Patent number
US06344476B1

Reaction notes

Loading…