Methyl iodide → (3R,4S)-3-butyl-3-methyl-4-pentyloxetan-2-one

HRID 13722Notes

Reaction equation

[CH2:1]([C@@H:5]1[C@@H:8]([CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[O:7][C:6]1=[O:14])[CH2:2][CH2:3][CH3:4].[Li+].[CH3:16][Si]([N-][Si](C)(C)C)(C)C.IC>C1COCC1>[CH2:1]([C@:5]1([CH3:16])[C@H:8]([CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[O:7][C:6]1=[O:14])[CH2:2][CH2:3][CH3:4]

Participants

Conditions

Temperature: -40 °C

Procedure

A solution of β-lactone 3a (36.3 mg, 0.1835 mmol) in 1.9 mL THF was cooled to −78° C. and 370 μL of LiHMDS (0.367 mmol, 2.0 equiv, 1.0 M solution in THF) was added under a nitrogen atmosphere. After 1.5 h, 23 μL (0.367 mmol, 2.0 equiv) of iodomethane was added and the reaction warmed to −40° C. and stirred for an additional 45 min. The reaction mixture was concentrated in vacuo and purified by flash chromatography (0→15% Et2O: hexanes) to give β-lactone 8a (28.4 mg, 73%) as a colorless oil and as a mixture of cis/trans diastereomers (dr, 6:1). Data provided for major diastereomer: Rf(15% Et2O:hexanes) 0.64; IR (thin film) 1824 cm−1; 1H NMR (500 MHz, CDCl3) δ 4.18 (dd (major diast.), J=6.0, 8.5Hz, 1H), 1.63-1.78 (m, 2H), 1.45-1.53 (m, 2H), 1.39 (s, 3H), 1.24-1.39 (m, 10H), 0.89-0.94 (m, 6H); 13C NMR (500 MHz, CDCl3) 14.1, 14.2, 20.0, 22.1, 25.5, 25.6, 26.5, 30.3, 31.7, 35.9, 56.8, 84.5, 175.5; ESI LRMS Calcd. for C13H24O2Li [M+Li]: 219. Found: 219.

Workup

concentrationThe reaction mixture was concentrated in vacuo
custompurified by flash chromatography (0→15% Et2O: hexanes)

Sources & evidence

ORD record: ord-99e75be609f4408a9abbe21eeeffbac9
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07728153B2

Reaction notes

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