Methyl chloroformate → 2-Propyl-4-(((2-tetrahydropyranyl)oxy)methyl)oxazole-5-carboxylic acid, methyl ester

HRID 235105Notes

Reaction equation

HRID 235105 reaction equation
Br[C:2]1[O:6][C:5]([CH2:7][CH2:8][CH3:9])=[N:4][C:3]=1[CH2:10][O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1.Cl[C:19]([O:21][CH3:22])=[O:20]>C1COCC1>[CH2:7]([C:5]1[O:6][C:2]([C:19]([O:21][CH3:22])=[O:20])=[C:3]([CH2:10][O:11][CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[N:4]=1)[CH2:8][CH3:9]

Participants

4

Reactant 2

HCID 6586Methyl chloroformateHCID 233535735-Bromo-2-propyl-4-(((2-tetrahydropyranyl)oxy)methyl)oxazole

Product 1

HCID 867502462-Propyl-4-(((2-tetrahydropyranyl)oxy)methyl)oxazole-5-carboxylic acid, methyl esterYield 74.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-bromo-2-propyl-4-(((2-tetrahydropyranyl)oxy)methyl)oxazole (2.376 g, 7.82 mmol), prepared as in Example 29c, in 60 mL of THF and cooled to -78° C. was added n-buthylithium (8.75 mmol). The resulting solution was stirred for 30 minutes at -78° C., and 1.0 mL (12.9 mmol) of methyl chloroformate was added. The reaction mixture was stirred at -78° C. for 5 minutes and at 0° for 30 minutes. The reaction was quenched by the addition of satd NaHCO3, the layers were separated, and the aqueous layer extracted with methylene chloride. The organic extracts were combined, dried, and concentrated. The residue was chromatographed on silica gel, eluting with 10 to 25% ethyl acetate in hexane, to afford 1.660 g of the title compound as an oil. MS m/z: 284 (M+H)+. NMR (CDCl3) δ:4.95 (d, J=12 Hz, 1H), 4.82 (t, J=3 Hz, 1H), 4.67 (d, J=12 Hz, 1H), 3.94 (m, 1H), 3.92 (s, 3H), 3.57 (m, 1H), 2.80 (t, J=7.5 Hz, 2H), 1.84 (sextet, J=7.5 Hz, 2H), 1.80-1.50 (m, 6H), 1.05 (t, J=7.5 Hz, 3H).

Workup

  1. additionwas added n-buthylithium (8.75 mmol)
  2. stirringThe reaction mixture was stirred at -78° C. for 5 minutes and at 0° for 30 minutes
  3. customThe reaction was quenched by the addition of satd NaHCO3
  4. customthe layers were separated
  5. extractionthe aqueous layer extracted with methylene chloride
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was chromatographed on silica gel
  9. washeluting with 10 to 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-83626b377bf447fca4da5228b28b9770
Source dataset
uspto-grants-1997_01
Patent number
US05597832

Reaction notes

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