Ammonium Chloride → HCID 11024440, compound

HRID 1871448Notes

Reaction equation

HRID 1871448 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)[CH:3]=1.[Li]CCCC.[C@@H:21]12[C:30](=[O:31])[O:29][C:27](=[O:28])[C@@H:22]1[CH2:23][CH2:24][CH2:25][CH2:26]2.[Cl-].[NH4+]>C1COCC1.O>[CH:11]1([O:10][C:4]2[CH:3]=[C:2]([CH:7]=[CH:6][C:5]=2[O:8][CH3:9])[C:30]([C@H:21]2[CH2:26][CH2:25][CH2:24][CH2:23][C@H:22]2[C:27]([OH:29])=[O:28])=[O:31])[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 641660Hexahydrophthalic anhydride, cis-HCID 99703924-Bromo-2-(cyclopentyloxy)-1-methoxybenzeneHCID 178418339Butyllithium

Product 1

HCID 11024440HCID 11024440, compoundYield 48.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-90 °C

Procedure

4-Bromo-2-cyclopentyloxy-1-methoxybenzene (16.3 g, 60 mmol) was dissolved in THF (200 ml) and cooled with an ethanol/N2 bath to -90° C. BuLi (41 ml, 66 mmol) was added dropwise while keeping the temperature below -80° C. and stirred for another 15 min after the last addition. This mixture was then quickly added under a nitrogen atmosphere to a cooled solution (-90° C.) of cis-1,2-cyclohexanedicarboxylic anhydride (11.1 g, 72 mmol) in THF (200 ml). After stirring for 2 h at -80° C. solid ammoniumchloride was added and the reaction mixture was allowed to warm slowly to room temperature. Water (300 ml) was added and the anorganic layer was washed with ethyl acetate (200 ml). The combined organic extracts were washed with water (300 ml) and brine (2×300 ml), dried (MgSO4) and the solvent removed under reduced pressure. The residue was dissolved in dichloromethane and purified by chromatography (petroleum ether (60°-95° C.)/ethyl acetate: 7/13) and crystallized from petroleum ether (60°-95° C.)/ethyl acetate to give the title compound (10.1 g) as a white solid. M.p. 120°-121° C.

Workup

  1. customthe temperature below -80° C.
  2. additionafter the last addition
  3. additionwas added
  4. temperatureto warm slowly to room temperature
  5. washthe anorganic layer was washed with ethyl acetate (200 ml)
  6. washThe combined organic extracts were washed with water (300 ml) and brine (2×300 ml)
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed under reduced pressure
  9. dissolutionThe residue was dissolved in dichloromethane
  10. custompurified by chromatography (petroleum ether (60°-95° C.)/ethyl acetate: 7/13)
  11. customcrystallized from petroleum ether (60°-95° C.)/ethyl acetate

Sources & evidence

ORD record
ord-005dd2840a0a4f98af0fd847cba5807b
Source dataset
uspto-grants-2000_08
Patent number
US06103718

Reaction notes

Loading…