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

Temperature

-78 °C

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) of 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 3×30 ml of pentane. The organic extracts were combined and washed successively with 2×30 ml of dilute HCl, water, 3×30 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 (6 H, s), 1.32 (6 H, s), 1.50 (2 H, s), 3.00 (1 H, s), 6.72 (1 H, d, J~8.4 Hz), 7.20 (1 H, dd, J~8.4 Hz, 2.1 Hz), 7.42 (1 H, d, J~2.1 Hz). MS exact mass, m/e 2.14.1251 (calcd. for C15H18O, 214.1357)

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. custom[prepared
6. customThe cooling bath was removed
7. stirringthe mixture was stirred at room temperature for 16 h
8. additionThe mixture was then treated with 10 ml of ice water
9. customThe organic layer was separated
10. extractionthe aqueous layer was extracted with 3×30 ml of pentane
11. washwashed successively with 2×30 ml of dilute HCl, water, 3×30 ml of saturated NaHCO3 solution and saturated NaCl solution
12. dry with materialdried (MgSO4)
13. customThe solvent was removed in vacuo
14. customthe residue was purified by flash chromatography (silica; 2% ethyl acetate in hexane)

ORD record

ord-f0fb162a59894cb2a33e49f80ddf5a47

Source dataset

uspto-grants-1994_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05278318