Acetyl chloride → methyl (1R,3S)-3-acetyl-2,2-dimethylcyclobutanecarboxylate

HRID 928093Notes

Reaction equation

[C:1](Cl)(=O)C.[C:5]([C@H:8]1[CH2:11][C@@H:10]([C:12]([OH:14])=[O:13])[C:9]1([CH3:16])[CH3:15])(=[O:7])[CH3:6]>CO>[C:5]([C@H:8]1[CH2:11][C@@H:10]([C:12]([O:14][CH3:1])=[O:13])[C:9]1([CH3:16])[CH3:15])(=[O:7])[CH3:6]

Participants

Conditions

Temperature: 0 °C

Procedure

Acetyl chloride (1.02 ml, 14.32 mmol) was added dropwise to MeOH (10 mL) at 0° C. and the resulting mixture was stirred at 0° C. for 30 mins. (1R,3S)-3-acetyl-2,2-dimethylcyclobutanecarboxylic acid from Step 1 (696 mg, 4.09 mmol) was added as a solution in MeOH (2 mL) and the reaction mixture was stirred overnight while warming up to room temperature. The volatiles were then removed under reduced pressure and the residue was purified by flash chromatography on silica gel (gradient elution, 2% to 20% EtOAc in Hexanes) to give methyl (1R,3S)-3-acetyl-2,2-dimethylcyclobutanecarboxylate as a colorless oil. MS ESI calc'd. for C10H17O3 [M+H]+ 185. found 185. 1H NMR (500 MHz, CDCl3) δ 3.66 (s, 3H), 2.88 (dd, J=10.5, 7.6 Hz, 1H), 2.78 (dd, J=10.8, 8.1 Hz, 1H), 2.64 (app q, J=10.8 Hz, 1H), 2.06 (s, 3H), 1.92-1.87 (m, 1H), 1.43 (s, 3H), 0.89 (s, 3H).

Workup

stirringthe reaction mixture was stirred overnight
temperaturewhile warming up to room temperature
customThe volatiles were then removed under reduced pressure
customthe residue was purified by flash chromatography on silica gel (gradient elution, 2% to 20% EtOAc in Hexanes)

Sources & evidence

ORD record: ord-6ba2103943ab4c4f9a241ba6ff74111a
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09290490B2

Reaction notes

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