Methyl iodide → HCID 68867449, compound

HRID 1985185Notes

Reaction equation

HRID 1985185 reaction equation
[CH2:1]([O:3][C:4](=[O:41])[C:5]([CH3:40])([O:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][CH:16]2[CH2:20][N:19]([CH2:21][C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)[C:18](=[O:32])[NH:17]2)=[CH:9][CH:8]=1)[CH3:2].[H-].[Na+].I[CH3:45]>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:41])[C:5]([CH3:40])([O:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:14][CH2:15][CH:16]2[CH2:20][N:19]([CH2:21][C:22]3[CH:31]=[CH:30][C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[CH:23]=3)[C:18](=[O:32])[N:17]2[CH3:45])=[CH:11][CH:12]=1)[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 68867189HCID 68867189, compound

Product 1

HCID 68867449HCID 68867449, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of a diasteriomeric mixture of 2-methyl-3-{4-[2-(1-naphthalen-2-ylmethyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester (0.275 g, 0.498 mmol) in DMF (7 mL) is treated with NaH (60% oil suspension, 0.030 g, 0.750 mmol) and stirred at room temperature under N2 for 30 minutes. The reaction is cooled to 0° C. and treated with iodomethane (0.141 g, 0.996 mmol) and then warmed to room temperature and stirred for 3 hours. The reaction is quenched with 1 N HCl (5 mL) and worked up extractively with Et2O and water. The organic layer is dried and the solvent removed in vacuo to afford crude product that is purified by flash chromatography using 4:1 hexanes:acetone to afford 0.268 g (95%) 2-methyl-3-{4-[2-(3-methyl-1-naphthalen-2-ylmethyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester. The diasteriomeric products are separated by chiral HPLC (8×32 cm Chiralpak AD, 100% IPA, 350 mL/min, 270 nm, to give products in>99% de 1H NMR. Rf=0.35 (1:1 acetone:hexanes). MS (ES+) Calc'd for C35H39N2O5 (M+1) 567. Found m/z 567 (100%).

Workup

  1. temperatureThe reaction is cooled to 0° C.
  2. temperaturewarmed to room temperature
  3. stirringstirred for 3 hours
  4. customThe reaction is quenched with 1 N HCl (5 mL)
  5. customThe organic layer is dried
  6. customthe solvent removed in vacuo
  7. customto afford crude product that
  8. customis purified by flash chromatography

Sources & evidence

ORD record
ord-6fd7f69bb56444a1a9f8eca9d7fd87d4
Source dataset
uspto-grants-2009_06
Patent number
US07544812B2

Reaction notes

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