Ammonium Chloride → 1,1-diethoxy-5-methyl-5-(tetrahydro-2H-pyran-2-yloxy)hex-3-yn-2-one

HRID 389290Notes

Reaction equation

HRID 389290 reaction equation
C([Li])CCC.[CH3:6][C:7]([O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1)([C:9]#[CH:10])[CH3:8].[CH2:18]([O:20][CH:21]([O:27][CH2:28][CH3:29])[C:22](OCC)=[O:23])[CH3:19].[NH4+].[Cl-]>CCOCC>[CH2:18]([O:20][CH:21]([O:27][CH2:28][CH3:29])[C:22](=[O:23])[C:10]#[C:9][C:7]([CH3:6])([O:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1)[CH3:8])[CH3:19]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 80169Ethyl diethoxyacetateHCID 41938432-Methyl-3-butyn-2-yl 2-tetrahydropyranyl etherHCID 178418339Butyllithium

Product 1

HCID 683253631,1-diethoxy-5-methyl-5-(tetrahydro-2H-pyran-2-yloxy)hex-3-yn-2-one

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-78 °C

Procedure

In a 250 mL round bottom flask, 9.5 mL of n-butyl lithium (2.5 M solution in hexane, 23.8 mmol) was added via a syringe to a pre-cooled solution (−78° C.) of 2-(2-methylbut-3-yn-2-yloxy)-tetrahydro-2H-pyran 2 (4.0 g, 23.8 mmol) in 100 mL of Et2O. The resulting solution was stirred for 30 min at −78° C., then ethyl 2,2-diethoxyacetate (4.9 g, 27.7 mmol) was added with a syringe, and the stirring continued for 12 hours. The reaction mixture was poured in an ice-cold saturated aqueous solution of NH4Cl. The aqueous layer was extracted with Et2O (3×50 mL). The organic solvent was separated with a separating funnel and dried with anhydrous MgSO4. The solvent was removed under reduced pressure and the resulting pale yellow oil was purified by radial chromatography (stationary phase silica gel, hexane/AcOEt 90:10) to provide 1,1-diethoxy-5-methyl-5-(tetrahydro-2H-pyran-2-yloxy)hex-3-yn-2-one 3 as a colorless liquid. Yield: 3.2 g (10.7 mmol; 45%). 1H-NMR in CDCl3 (δ, ppm): 5.05 (1H, q, J=5.0, 3.5 Hz, THP), 4.73 (1H, s, acetal), 3.92 (1H, m, THP), 3.69 (2H, m, CH2, acetal), 3.62 (2H, m, CH2, acetal), 3.50 (1H, m, THP), 1.82 (1H, m, THP), 1.71 (1H, m, THP), 1.58 (3H, s, CH3), 1.54 (3H, s, CH3), 1.52 (4H, m, THP), 1.25 (6H, t, J=7.0 Hz, CH3, acetal). 13C-NMR in CDCl3 (δ, ppm): 182.6, 101.1, 97.87, 96.10, 81.25, 70.57, 62.95, 62.64, 62.61, 31.47, 29.45, 28.85, 25.06, 19.92, 14.90 IR (neat, cm−1): 2978, 2937, 2872, 2214, 1687, 1074. HR ESIMS+ with acetonitrile as the mobile phase, (m/z): 299.1837 (M+, C16H26O5, 299.1853), 321.1660 (m/z) ([M+Na]+, C16H26O5Na, 321.1672).

Workup

  1. waitthe stirring continued for 12 hours
  2. extractionThe aqueous layer was extracted with Et2O (3×50 mL)
  3. customThe organic solvent was separated with a separating funnel
  4. dry with materialdried with anhydrous MgSO4
  5. customThe solvent was removed under reduced pressure
  6. customthe resulting pale yellow oil was purified by radial chromatography (stationary phase silica gel, hexane/AcOEt 90:10)

Sources & evidence

ORD record
ord-b1af128c8f6b4dac916260a9cd7da5a0
Source dataset
uspto-grants-2013_02
Patent number
US08378123B2

Reaction notes

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