Methoxymethyl-triphenylphosphonium chloride → 4-[5-(2-Methoxy-vinyl)-imidazole-1-yl]-3,3-dimethyl-isochroman-1-one

HRID 1690730Notes

Reaction equation

[Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[CH3:34][C:35]1([CH3:53])[CH:44]([N:45]2[C:49]([CH:50]=O)=[CH:48][N:47]=[CH:46]2)[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:37](=[O:52])[O:36]1>C1COCC1>[CH3:2][O:3][CH:4]=[CH:50][C:49]1[N:45]([CH:44]2[C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[C:37](=[O:52])[O:36][C:35]2([CH3:53])[CH3:34])[CH:46]=[N:47][CH:48]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of methoxymethyltriphenylphosphonium chloride (0.974 g, 2.84 mmol) in THF (10 mL) at −78° C. is added sodium hexamethyldisilazide (1M in THF, 3.0 mL, 3.09 mmol) and the mixture is stirred at −78° C. for 1 h. 3-(3,3-dimethyl-1-oxo-isochroman-4-yl)-3H-imidazole-4-carbaldehyde (0.10 g, 0.37 mmol) (Example 9a) in THF (0.2 mL) is then added at −78° C. and the mixture is stirred at ambient temperature overnight. It is then quenched with water and extracted with ethyl acetate. The organic phase is concentrated in vacuo. The residue is purified using by semi-preparative reverse phase HPLC to afford 4-[5-(2-methoxy-vinyl)-imidazole-1-yl]-3,3-dimethyl-isochroman-1-one; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31 (s, 3 H), 1.52 (s, 3 H), 3.75 (br. s, 3 H), 5.22 (s, 1 H), 5.31 (s, 1 H), 5.55 (br. s, 1 H), 6.82 (br. s, 1 H), 6.96 (br. s, 1 H), 7.16 (d, J=7.6 Hz, 1 H), 7.55 (td, J=7.6, 1.3 Hz, 1 H), 7.63 (td, J=7.6, 1.3 Hz, 1 H), 8.24 (dd, J=7.7, 1.4 Hz, 1 H).

Workup

stirringthe mixture is stirred at ambient temperature overnight
customIt is then quenched with water
extractionextracted with ethyl acetate
concentrationThe organic phase is concentrated in vacuo
customThe residue is purified

Sources & evidence

ORD record: ord-f4e6555221c041058b977c61203200d0
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153674B2

Reaction notes

Loading…