Methyl iodide → HCID 42635719, compound

HRID 1674681Notes

Reaction equation

HRID 1674681 reaction equation
[CH3:1]I.C(OC([N:10]1[CH2:15][C@H:14]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]3[O:26][CH2:25][CH2:24][N:23]([CH2:27][CH2:28][CH2:29][O:30][CH3:31])[C:22]=3[CH:32]=2)[C@@H:13]([C:33]2[CH:38]=[CH:37][C:36]([CH2:39][O:40][CH2:41][C@H:42]([O:44][CH2:45][CH3:46])[CH3:43])=[CH:35][CH:34]=2)[C@H:12]([CH2:47][OH:48])[CH2:11]1)=O)(C)(C)C.[H-].[Na+]>>[CH3:1][O:48][CH2:47][C@@H:12]1[CH2:11][NH:10][CH2:15][C@H:14]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]3[O:26][CH2:25][CH2:24][N:23]([CH2:27][CH2:28][CH2:29][O:30][CH3:31])[C:22]=3[CH:32]=2)[C@H:13]1[C:33]1[CH:38]=[CH:37][C:36]([CH2:39][O:40][CH2:41][C@H:42]([O:44][CH2:45][CH3:46])[CH3:43])=[CH:35][CH:34]=1

Participants

4

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 42609851HCID 42609851, compound

Product 1

HCID 42635719HCID 42635719, 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)-4-[4-((R)-2-ethoxy-propoxymethyl)-phenyl]-3-hydroxymethyl-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-piperidine-1-carboxylic acid tert-butyl ester (example 1a) and 0.963 mmol of NaH (60% dispersion in oil) under argon at 0° C. After stirring for 1 h at 0° C. and 1 h at RT, the reaction mixture is partitioned between TBME and saturated aqueous NaHCO3 solution. The aqueous layer is extracted with TBME (2×)—the combined organic layers are washed successively with H2O and brine, dried with Na2SO4 and evaporated. The residue is purified by flash chromatography (SiO2 60F) to afford the title compound, which is identified based on the Rf value.

Workup

  1. customthe reaction mixture is partitioned between TBME and saturated aqueous NaHCO3 solution
  2. extractionThe aqueous layer is extracted with TBME (2×)—the combined organic layers
  3. washare washed successively with H2O and brine
  4. dry with materialdried with Na2SO4
  5. customevaporated
  6. customThe residue is purified by flash chromatography (SiO2 60F)

Sources & evidence

ORD record
ord-eedafe75ce984edfa15e8dfbe4ff2e4b
Source dataset
uspto-grants-2011_08
Patent number
US08003640B2

Reaction notes

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