Methyl iodide → HCID 66877348, compound

HRID 1863980Notes

Reaction equation

HRID 1863980 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]=1

Participants

4

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66877910HCID 66877910, compound

Product 1

HCID 66877348HCID 66877348, compound

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).

Workup

  1. customthe reaction mixture is partitioned between tert-butyl methyl ether and saturated aqueous sodium bicarbonate solution
  2. extractionThe aqueous layer is extracted with tert-butyl methyl ether (2×)—the combined organic layers
  3. washare washed successively with water and brine
  4. dry with materialdried with sodium sulfate
  5. customevaporated
  6. customThe residue is purified by flash chromatography (SiO2 60F)

Sources & evidence

ORD record
ord-ba373f1ffd55454ab05966938ab01696
Source dataset
uspto-grants-2009_12
Patent number
US07625893B2

Reaction notes

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