Methyl iodide → HCID 178498321, compound

HRID 1434881Notes

Reaction equation

[CH3:1][S:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([O:13][C@H:14]2[CH2:19][CH2:18][C@@H:17]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16][CH2:15]2)[CH:4]=1.[CH3:28][Si](C)(C)[N-][Si](C)(C)C.[Li+].CI>C1COCC1>[CH3:1][S:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([O:13][C@H:14]2[CH2:19][CH2:18][C@@H:17]([N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH3:28])[CH2:16][CH2:15]2)[CH:4]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a mixture of methyl 4-methylthio-2-[cis-4-(t-butoxy-carbonylamino)cyclohexyloxy]benzoate (3.0 g, 7.59 mmol) in THF (15 mL) at −20° C. was added 1 M lithium hexamethyl-disilazide (LiHMDS)/hexane (8.0 ml, 7.97 mmol, 1.05 eq), and the mixture was warmed to 0° C. for 10 min. To the reaction mixture was added methyl iodide (0.5 mL, 7.97 mmol, 1.05 equivalent), the mixture was warmed to room temperature and stirred for 7 h, and the reaction was quenched with satd citric acid. The mixture was diluted with CH2Cl2 and partitioned. The organic layer was dried (Na2SO4) and concentrated. This material was combined with the crude product from a small scaled reaction (500 mg, 1.27 mmol), chromatographed (400 g, SiO2, hexanes to 20% EtOAc/hexanes) and triturated with Et2O to give the title compound as a white solid (1.3 g, 36%).

Workup

temperaturethe mixture was warmed to room temperature
customthe reaction was quenched with satd citric acid
additionThe mixture was diluted with CH2Cl2
custompartitioned
dry with materialThe organic layer was dried (Na2SO4)
concentrationconcentrated
customreaction (500 mg, 1.27 mmol)
customchromatographed (400 g, SiO2, hexanes to 20% EtOAc/hexanes)
customtriturated with Et2O

Sources & evidence

ORD record: ord-85531c5542fb4c348515180408b11aa6
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07615568B2

Reaction notes

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