Diisopropylamine → 2,2,4,4-Tetramethyl-6-ethynylchroman

HRID 1734726Notes

Reaction equation

HRID 1734726 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1([CH3:29])[CH2:23][C:22]([CH3:25])([CH3:24])[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:26](=O)[CH3:27])[CH:20]=2)[O:15]1.C(OP(Cl)(OCC)=O)C.C([N-]C(C)C)(C)C.[Li+]>C1COCC1.CCCCCC>[CH3:13][C:14]1([CH3:29])[CH2:23][C:22]([CH3:24])([CH3:25])[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:26]#[CH:27])[CH:20]=2)[O:15]1

Participants

8

Reactant 5

HCID 7912Diisopropylamine2×HCID 13139Diethyl chlorophosphateHCID 2724682Lithium diisopropylamideHCID 156611361-(2,2,4,4-Tetramethyl-3,4-dihydro-2H-1-benzopyran-6-yl)ethan-1-one2×HCID 178418339Butyllithium2×

Product 1

HCID 156611382,2,4,4-Tetramethyl-6-ethynylchroman

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a cooled (-78 degrees C.) solution of 522 mg (5.17 mmol) of diisopropylamine in 8 ml of dry THF was added slowly, under nitrogen, 3.23 ml of 1.6M (5.17 mmol) n-butyl lithium in hexane. The mixture was stirred at -78 degrees C. for 40 minutes and then treated with a solution of 1.24 g (5.17 mmol) of 2,2,4,4-tetramethyl-6-acetylchroman (Compound 41) in 2 ml of dry THF. The mixture was stirred at -78 degrees C. for a further 1 h and then treated with 895 mg (5.19 mmol) of diethylchlorophosphate. The reaction mixture was allowed to warm to room temperature and transferred by double-ended needle into a solution of lithium diisopropylamide in THF at -78 degrees C. [prepared as described above from 1.04 g (10.34 mmol) of diisopropylamine and 6.46 ml of 1.6M (10.34 mmol) n-butyl lithium in hexane]. The cooling bath was removed and the mixture was stirred at room temperature for 16 h. The mixture was then treated with 10 ml of ice water and acidified to a pH of 2 with 10% HCl. The organic layer was separated and the aqueous layer was extracted with 3x30 ml of pentane. The organic extracts were combined and washed successively with 2x30 ml of dilute HCl, water, 3x30 ml of saturated NaHCO3 solution and saturated NaCl solution and then dried (MgSO4). The solvent was removed in vacuo and the residue was purified by flash chromatography (silica; 2% ethyl acetate in hexane) to give the title compound as a pale yellow oil. PMR (CDCl3 ): & 1.31 (6H, s), 1.32 (6H, s), 1.50 (2H, s), 3.00 (1a, s), 6.72 (1H, d, J-8.4 Hz), 7.20 (1H, dd, J-8.4 Hz, 2.1 Hz), 7.42 (1H, d, J-2.1 Hz). MS exact mass, m/e 214.1251 (calcd. for C15H18O, 214.1357).

Workup

  1. additionwas added slowly, under nitrogen
  2. stirringThe mixture was stirred at -78 degrees C
  3. waitfor a further 1 h
  4. temperatureto warm to room temperature
  5. customThe cooling bath was removed
  6. stirringthe mixture was stirred at room temperature for 16 h
  7. additionThe mixture was then treated with 10 ml of ice water
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was extracted with 3x30 ml of pentane
  10. washwashed successively with 2x30 ml of dilute HCl, water, 3x30 ml of saturated NaHCO3 solution and saturated NaCl solution
  11. dry with materialdried (MgSO4)
  12. customThe solvent was removed in vacuo
  13. customthe residue was purified by flash chromatography (silica; 2% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-41c069dc94554ac5b228090eb9ffdfc7
Source dataset
uspto-grants-1996_07
Patent number
US05534516

Reaction notes

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