Hydrochloric Acid → 2,2,4,4,7-Pentamethyl-6-ethynyl-chroman

HRID 6552

Reaction equation

HRID 6552 reaction equation
[Li]CCCC.[CH3:6][C:7]1([CH3:23])[CH2:16][C:15]([CH3:18])([CH3:17])[C:14]2[C:9](=[CH:10][C:11]([CH3:22])=[C:12]([C:19](=O)[CH3:20])[CH:13]=2)[O:8]1.P(Cl)(OCC)(OCC)=O.C([N-]C(C)C)(C)C.[Li+].C(NC(C)C)(C)C.Cl>C1COCC1.CCCCCC.O>[CH3:6][C:7]1([CH3:23])[CH2:16][C:15]([CH3:17])([CH3:18])[C:14]2[C:9](=[CH:10][C:11]([CH3:22])=[C:12]([C:19]#[CH:20])[CH:13]=2)[O:8]1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 13139Diethyl chlorophosphateHCID 2724682Lithium diisopropylamideHCID 156611372,2,4,4,7-Pentamethyl-6-acetylchroman2×HCID 178418339Butyllithium2×

Product 1

HCID 156611392,2,4,4,7-Pentamethyl-6-ethynyl-chroman

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 455 mg (4.5 mmol) of disopropylamine in 5 ml of dry THF at -78 degrees C. was added under argon 3 ml of 1.5 M n-BuLi in hexane. The mixture was stirred at -78 degrees C. for a further 45 min and then treated with a solution of 1.07 g (4.3 mmol) of 2,2,4,4,7-pentamethyl-6-acetyl-chroman (Compound 90) in 4 ml of dry THF. The reaction mixture was stirred at -78 degrees C. for 1 h and then treated with 776 mg (4.5 mmol) of diethyl chlorophosphate. The mixture was allowed to warm to room temperature and then transferred by a double-ended needle into a solution of lithium diisopropyl amide in 10 ml dry THF at -78 degrees C. which was prepared as described above using 910 mg (9.0 mmol) of diisopropylamine and 6 ml of 1.5 M (9.0 mmol) n-BuLi in hexane. The mixture was stirred at room temperature for 15 h and then poured into 10 ml of iced water The mixture was acidified to pH=2 with 10% HCl solution. The organic layer was separated and the aqueous layer extracted with pentane. The organic extracts were combined and washed successively with water, saturated NaHCO3 and saturated NaCl solutions and then dried (MgSO4). The solvent was removed in vacuo and the residue purified by Kugelrohr distillation (82 degrees C. 0.3 mm) to give the title compound as a pale yellow oil. PMR (CDCl3): δ 1.32 (6H, s), 1.34 (6H, s), 1.81 (2H, s), 2.36 (3H, s), 3.18 (1H, s), 6.64 (1H, s), 7.40 1H (s). MS exact mass, m/e 228.1520 (calcd. for C16H20O, 228.1514).

Workup

  1. customat -78 degrees C
  2. stirringThe reaction mixture was stirred at -78 degrees C
  3. waitfor 1 h
  4. temperatureto warm to room temperature
  5. customwhich was prepared
  6. stirringThe mixture was stirred at room temperature for 15 h
  7. customThe organic layer was separated
  8. extractionthe aqueous layer extracted with pentane
  9. washwashed successively with water, saturated NaHCO3 and saturated NaCl solutions
  10. dry with materialdried (MgSO4)
  11. customThe solvent was removed in vacuo
  12. distillationthe residue purified by Kugelrohr distillation (82 degrees C. 0.3 mm)

Sources & evidence

ORD record
ord-8ab7f252cbf94f38a7c5fa1c66be5d0f
Source dataset
uspto-grants-1993_09
Patent number
US05248777

Linked notes

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