Methyl iodide → HCID 58904451, compound

HRID 1292741Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1)[O:6][C@@H:7]([C@:11]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13][NH:12]1)[C:8]([OH:10])=[O:9].[CH2:32]1COCC1.Cl[Si](C)(C)C.CI>CC(=O)OCC>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1)[O:6][C@@H:7]([C@:11]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13][N:12]1[CH3:32])[C:8]([OH:10])=[O:9]

Participants

Conditions

Temperature: 55 °C

Procedure

To a suspension of (±)-(S*)-(3,5-dimethoxy-phenoxy)-((1S*)-1-phenyl-1,2,3,4-tetrahydro-isoquinolin-1-yl)-acetic acid (200 mg, 0.477 mmol, Example 1) in THF (5 ml) Hünig's base (327 μl, 1.91 mmol) followed by chlorotrimethylsilane (72 μl, 0.572 mmol) is added. The mixture is stirred at 55° C. for 3 h before methyliodide (30 μl, 0.477 mmol) is added. Stirring at 55° C. is continued for another 16 h. The mixture is diluted with EA and extracted with water. The aqueous phase is acidified with 2 N HCl and extracted with EA. The EA-phase is dried over Na2SO4 and evaporated. The crude product is purified by prep. HPLC on Rp-C18-silica gel to give (±)-(S*)-(3,5-dimethoxy-phenoxy)-((1S*)-2-methyl-1-phenyl-1,2,3,4-tetrahydro-isoquinolin-1-yl)-acetic acid (139 mg) as a white powder. LC-MS2: tR=4.03 min, [M+1]+=434.34, [M−1]−=432.32.

Workup

additionis added
additionis added
extractionextracted with water
extractionextracted with EA
dry with materialThe EA-phase is dried over Na2SO4
customevaporated
customThe crude product is purified by prep

Sources & evidence

ORD record: ord-ad96854889ed4d3cbd3cb1d0c8f48315
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07238685B2

Reaction notes

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