Sodium Hydroxide → 6-Ethynyl-1,1,4,4-tetramethyl-7-propoxy-1,2,3,4-tetrahydronaphthalene

HRID 1265244Notes

Reaction equation

HRID 1265244 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([O:9][C:10]1[C:11]([C:24](=O)[CH3:25])=[CH:12][C:13]2[C:14]([CH3:23])([CH3:22])[CH2:15][CH2:16][C:17]([CH3:21])([CH3:20])[C:18]=2[CH:19]=1)[CH2:7][CH3:8].C([O-])(O)=O.[Na+].[OH-].[Na+]>O1CCOCC1.O.[Cl-].[Na+].O.O.O1CCOCC1.CN(C=O)C>[C:24]([C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][C:10]=1[O:9][CH2:6][CH2:7][CH3:8])[C:17]([CH3:21])([CH3:20])[CH2:16][CH2:15][C:14]2([CH3:22])[CH3:23])#[CH:25]

Participants

10

Reactant 4

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 101494431-(3-Propoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)ethanone

Product 1

HCID 106596866-Ethynyl-1,1,4,4-tetramethyl-7-propoxy-1,2,3,4-tetrahydronaphthaleneYield 39%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolventHCID 218864351,4-Dioxane--water (1/1)SolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

Phosphorous oxychloride (0.234 g, 0.142 mL, 1.52 mmol) was added dropwise to DMF (4 mL) at room temperature under a nitrogen atmosphere. The solution was stirred for 30 min. The 1-(3-propoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)ethanone, (prepared as described in Example 21, 0.110 g, 0.381 mmol) was added quickly (in one portion) to the orange solution and the reaction solution was heated to 60° C. and stirred for 12 h. The dark brown solution was poured into ice water and the aqueous layer was adjusted to pH 7 with solid NaHCO3. EtOAc extraction afforded the crude product, the chloro enal, 0.128 g, as an orange/brown oil. To a 80° C. solution of NaOH (0.061 g, 1.52 mmol) in dioxane: H2O (3:2; 20 mL) was added the crude chloro enal in a dioxane:water solution (3:2; 5 mL) in one portion and the yellow reaction solution was stirred at 80° C. for 2 h. The resulting orange reaction solution was cooled to room temperature and poured into brine and extracted with EtOAc. The organic solution was dried (MgSO4), filtered, and concentrated to afford an orange oil which was purified by radial chromatography (10:1=Hex:EtOAc) to give the product 6-ethynyl-1,1,4,4-tetramethyl-7-propoxy-1,2,3,4-tetrahydronapthalene 0.040 g (39%) as a yellow oil: 1H-NMR (400 MHz, CDCl3) δ 7.38 (s, 1H, Ar-H), 6.76 (s, 1Hz, Ar-H), 3.98 (t, J=6.6 Hz, 2H, OCH2), 3.19 (s, 1H, CH), 1.83 (m, 2Hz, CH2), 1.66 (m, 2H, 2CH2), 1.26 (s, 6H, 2CH3), 1.24 (s, 6H, 2CH3), 0.93 (t, J=7.4 Hz, 3H, CH3).

Workup

  1. additionwas added quickly (in one portion) to the orange solution
  2. stirringstirred for 12 h
  3. extractionEtOAc extraction
  4. customafforded the crude product
  5. temperatureThe resulting orange reaction solution was cooled to room temperature
  6. extractionextracted with EtOAc
  7. dry with materialThe organic solution was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford an orange oil which
  11. customwas purified by radial chromatography (10:1=Hex:EtOAc)

Sources & evidence

ORD record
ord-45f8780c778b44359dc892c2341818f9
Source dataset
uspto-grants-2003_04
Patent number
US06545049B1

Reaction notes

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