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

HRID 2420657Notes

Reaction equation

HRID 2420657 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+].OC(C1C=C2C(=CC=1OCCC)C(C)(C)CCC2(C)C)=CCl.[OH-].[Na+]>O1CCOCC1.O.[Cl-].[Na+].O.CN(C)C=O>[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

9

Reactant 5

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 101494431-(3-Propoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)ethanoneHCID 86595829Chloroenal2×

Product 1

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

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 218864351,4-Dioxane--water (1/1)Solvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

Phosphorus oxychloride (0.234 grams, 0.142 ml, 1.52 mmol) was added dropwise to dimethyl formamide (DMF) (4 ml) at room temperature under a nitrogen atmosphere. The solution was stirred for 30 minutes. The 1-(3-propoxy-5,6,7,8-tetrahydro-5,5,8,8,-tetramethylnaphthalen-2-yl)ethanone was added quickly (in one portion) to the orange solution, the reaction solution was heated to 60° C. and was stirred for 12 hours. The obtained dark brown solution was poured into ice water and the aqueous layer was adjusted to pH 7 with solid sodium hydrogen carbonate. Ethyl acetate extraction afforded the crude product, the chloroenal (6-[1-hydroxy,2-chloro-ethenyl]-1,1,4,4-tetramethyl-7-propoxy-1,2,3,4-tetrahydronaphthalene), 0.128 grams, as an orange/brown oil. A solution of the crude chloroenal in dioxane:water (3:2; 5 ml) was added to a solution of NaOH (0.061 grams, 1.52 mmol) in dioxane: H2O (3:2; 20 ml), at 80° C., and the reaction mixture was stirred for 2 hours, to yield an orange reaction solution. The reaction solution was cooled to room temperature, poured into brine and extracted with EtOAc. The organic phase was dried (MgSO4), filtered, and concentrated to afford an orange oil which was purified by radial chromatography (10:1 hexane:ethyl acetate) to give the product 6-ethynyl-1,1,4,4,-tetramethyl-7-propoxy-1,2,3,4-tetrahydronaphthalene (39%) as a yellow oil [1H-NMR (400 MHz, CDCl3): d 7.38(s, 1H, Ar—H), 6.76(s,1H, Ar—H), 3.98 (t, J=6.6 Hz, 2H, OCH3), 3.19 (s, 1H, CH),1.83 (m, 2H, CH2),1.66 (m, 2H, 2CH2),1.26 (s, 6H, 2CH3),1.23 (s, 6H, 2CH3), 0.93 (t, J=7.4 Hz, 3H, CH3)].

Workup

  1. stirringwas stirred for 12 hours
  2. extractionEthyl acetate extraction
  3. customafforded the crude product
  4. stirringthe reaction mixture was stirred for 2 hours
  5. customto yield an orange reaction solution
  6. temperatureThe reaction solution was cooled to room temperature
  7. extractionextracted with EtOAc
  8. dry with materialThe organic phase was dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford an orange oil which
  12. customwas purified by radial chromatography (10:1 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-4154946506cf4194bf5713fc0fa3cb38
Source dataset
uspto-grants-2011_06
Patent number
US07955852B2

Reaction notes

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