Hydrochloric Acid → tert-butyl 2-methyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]propanoate

HRID 530925Notes

Reaction equation

HRID 530925 reaction equation
[OH:1][C:2]([CH3:11])([CH3:10])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[H-].[Na+].Br[CH2:15][CH2:16][CH2:17][O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1.Cl>CN(C)C=O.O>[CH3:10][C:2]([O:1][CH2:15][CH2:16][CH2:17][O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)([CH3:11])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 118940tert-Butyl 2-hydroxyisobutyrateHCID 27779882-(3-Bromopropoxy)tetrahydro-2H-pyran

Product 1

HCID 66588004tert-butyl 2-methyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]propanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution (22 mL) of tert-butyl 2-hydroxy-2-methylpropanoate (1.0 g) in N,N-dimethylformamide was added sodium hydride (250 mg) under an ice bath, and the mixture was stirred at room temperature for 1 hour. Thereafter, under an ice bath, 2-(3-bromopropoxy)tetrahydro-2H-pyran (0.88 mL) was added dropwise, and the mixture was stirred at room temperature overnight. To the reaction mixture were added water and 1N hydrochloric acid under an ice bath, followed by extraction with t-butyl methyl ether. The organic layer was sequentially washed with an aqueous saturated sodium bicarbonate solution and an aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1) to obtain the title compound having the following physical property values, as a mixture (400 mg) with tert-butyl 2-hydroxy-2-methylpropanoate.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractionfollowed by extraction with t-butyl methyl ether
  3. washThe organic layer was sequentially washed with an aqueous saturated sodium bicarbonate solution
  4. dry with materialan aqueous saturated sodium chloride solution, dried with anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1)

Sources & evidence

ORD record
ord-9347194995ad4601bca5cbd3d26fe037
Source dataset
uspto-grants-2016_05
Patent number
US09353113B2

Reaction notes

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