Methyl iodide → HCID 66877348, compound
Reaction equation
[CH3:1]I.[CH2:3]([O:10][C:11]([N:13]1[CH2:18][C@H:17]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][C:24]3[O:29][CH2:28][CH2:27][N:26]([CH2:30][CH2:31][CH2:32][O:33][CH3:34])[C:25]=3[CH:35]=2)[C@@H:16]([C:36]2[CH:41]=[CH:40][C:39]([CH2:42][O:43][CH2:44][C@@H:45]([CH3:49])[CH2:46][O:47][CH3:48])=[CH:38][CH:37]=2)[C@H:15]([CH2:50][OH:51])[CH2:14]1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[H-].[Na+]>>[CH2:3]([O:10][C:11]([N:13]1[CH2:18][C@H:17]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][C:24]3[O:29][CH2:28][CH2:27][N:26]([CH2:30][CH2:31][CH2:32][O:33][CH3:34])[C:25]=3[CH:35]=2)[C@@H:16]([C:36]2[CH:41]=[CH:40][C:39]([CH2:42][O:43][CH2:44][C@@H:45]([CH3:49])[CH2:46][O:47][CH3:48])=[CH:38][CH:37]=2)[C@H:15]([CH2:50][O:51][CH3:1])[CH2:14]1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1Participants
4
Conditions
- Temperature
- 0 °C
Procedure
2.568 mmol of methyl iodide are added to a suspension of 0.642 mmol of (3S,4R,5R)-3-hydroxymethyl-4-[4-((S)-3-methoxy-2-methyl-propoxymethyl)-phenyl]-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-piperidine-1-carboxylic acid benzyl ester (Example 1a) and 0.963 mmol of sodium hydride (60% dispersion in oil) under argon at 0° C. After stirring for 1 hour at 0° C. and 1 hour at room temperature, the reaction mixture is partitioned between tert-butyl methyl ether and saturated aqueous sodium bicarbonate solution. The aqueous layer is extracted with tert-butyl methyl ether (2×)—the combined organic layers are washed successively with water and brine, dried with sodium sulfate and evaporated. The residue is purified by flash chromatography (SiO2 60F) to afford the title compound as a yellow oil. Rf=0.41 (EtOAc-heptane 1:1); Rt=5.87 (gradient I).