Acetone → HCID 10495806, compound

HRID 1872855Notes

Reaction equation

HRID 1872855 reaction equation
[C:1]([C:5]1[C:14]2[O:13][CH2:12][CH2:11][C:10]([CH3:16])([CH3:15])[C:9]=2[CH:8]=[C:7]([C:17](=[O:19])[CH3:18])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.CCN(C(C)C)C(C)C.[CH3:41][C:42]([CH3:44])=[O:43].Cl>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[C:1]([C:5]1[C:14]2[O:13][CH2:12][CH2:11][C:10]([CH3:16])([CH3:15])[C:9]=2[CH:8]=[C:7]([C:17](=[O:19])[CH2:18][C:42]([OH:43])([CH3:44])[CH3:41])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 65367Trimethylsilyl triflateHCID 81531DiisopropylethylamineHCID 18687694HCID 18687694, compound

Product 1

HCID 10495806HCID 10495806, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a cold (-78° C.) solution of 1-(8-tert-butyl-4,4-dimethyl-2,3-dihydrobenzopyran-6-yl)1-ethanone (0.35 g, 1.36 mmol) in CH2Cl2 (3.0 mL) is added TMSOTf (0.32 mL, 1.63 mmol, 1.2 equiv) and (i-Pr)2NEt (0.28 mL, 1.63 mmol, 1.2 equiv) dropwise. The resulting red mixture is stirred at -78° C. for 30 min, and then allowed to warm to room temperature over 1 h. The resulting pale red solution is recooled to -78° C. and acetone (0.12 mL, 1.63 mmol, 1.2 equiv) and TiCl4 (0.15 mL, 1.36 mmol, 1.0 equiv) are added dropwise. The resulting deep red solution is allowed to warm to room temperature over 3.5 h and 0.5N HCl is added and the mixture is stirred for 30 min. The reaction mixture is diluted with hexanes and washed with water and brine. The aqueous layers are extracted with hexanes; the combined organic layers are dried (MgSO4), filtered and concentrated. The residue is purified by flash column chromatography on silica (hexanes, hexanes/EtOAc; 10/1) to give the title compound (0.30 g, 70%) as a pale yellow solid which is recrystallized using pentane.

Workup

  1. temperatureto warm to room temperature over 1 h
  2. customis recooled to -78° C.
  3. temperatureto warm to room temperature over 3.5 h
  4. stirringthe mixture is stirred for 30 min
  5. washwashed with water and brine
  6. extractionThe aqueous layers are extracted with hexanes
  7. dry with materialthe combined organic layers are dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue is purified by flash column chromatography on silica (hexanes, hexanes/EtOAc; 10/1)

Sources & evidence

ORD record
ord-a8a79e2f26454532bfcd58c4ff128a4b
Source dataset
uspto-grants-2000_08
Patent number
US06110960

Reaction notes

Loading…