Chloroacetic Acid → 2-(2-((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)ethoxy)acetic acid

HRID 1912516Notes

Reaction equation

[CH3:1][C:2]1([CH3:12])[CH:7]2[CH2:8][CH:3]1[CH2:4][CH:5]=[C:6]2[CH2:9][CH2:10][OH:11].[H-].[Na+].Cl[CH2:16][C:17]([OH:19])=[O:18].[OH-].[Na+]>C(COC)OC.O>[CH3:1][C:2]1([CH3:12])[C@H:7]2[CH2:8][C@@H:3]1[CH2:4][CH:5]=[C:6]2[CH2:9][CH2:10][O:11][CH2:16][C:17]([OH:19])=[O:18]

Participants

Conditions

Temperature: 45 °C

Procedure

To a solution of (−)-nopol (Aldrich) (100 g, 0.60 mmol) in dimethoxy ethane (350 mL) was added NaH (60% oil dispersion, 31.1 g, 0.81 mmol). The mixture was refluxed for 2.5 hours, cooled to 45° C., and 2-chloroacetic acid (23.5 g 0.25 mmol) in dimethoxy ethane (180 mL) was added drop wise over a period of 1.5 hours. The reaction mixture was refluxed for 1 hour. After cooling at room temperature, water (75 mL) was added slowly, followed by 10% aqueous NaOH. The mixture was extracted with ether (1 L) (discarded), the aqueous phase was acidified and extracted with ether. The organic layer was dried over magnesium sulfate, filtered, and concentrated. The residue was distilled under reduced pressure to yield the title compound (29.5 g, 135-137° C. at 1.0 mm of Hg). n25D 1.4914, mp 78-80° C.

Workup

temperatureThe mixture was refluxed for 2.5 hours
temperatureThe reaction mixture was refluxed for 1 hour
temperatureAfter cooling at room temperature
extractionThe mixture was extracted with ether (1 L) (discarded)
extractionextracted with ether
dry with materialThe organic layer was dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
distillationThe residue was distilled under reduced pressure

Sources & evidence

ORD record: ord-58b4b86386ab405fb9dcf8eb5728eaee
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08609674B2

Reaction notes

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