Methyl iodide → HCID 67208792, compound

HRID 70912Notes

Reaction equation

HRID 70912 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C@H:4]([OH:28])[CH:5]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)=[CH:9][CH:8]=1.I[CH3:31]>CC#N.[Ag]=O>[CH3:1][O:2][C:3](=[O:29])[C@H:4]([O:28][CH3:31])[CH:5]([NH:20][C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)=[CH:9][CH:8]=1

Participants

5

Reactant 2

HCID 6328Methyl iodide2×HCID 67208772(R)-3-tert-butoxycarbonylamino-4-(3'-chloro-biphenyl-4-yl)-2-hydroxy-butyric acid methyl ester

Product 1

HCID 67208792HCID 67208792, compoundYield 79.5%

Reagents, catalysts & solvents 2

HCID 92152Silver(II) oxideCatalyst2×HCID 6342AcetonitrileSolvent

Procedure

To a solution of (R)-3-tert-butoxycarbonylamino-4-(3′-chloro-biphenyl-4-yl)-2-hydroxy-butyric acid methyl ester (610 mg, 1.45 mmol) in CH3CN (20 mL) are added iodomethane (0.545 mL, 8.72 mmol) and silver oxide (1.35 g, 5.81 mmol). After being stirred at room temperature for 16 h, additional iodomethane (0.545 mL, 8.72 mmol) and silver oxide (1.35 g, 5.81 mmol) are added and stirred for 3 days. The reaction mixture is filtered through celite pad and the filtrate is washed with brine. The organic layer is dried over MgSO4 and concentrated. The residue is purified by flash column chromatography (silica gel, eluent; heptane/EtOAc=100:0 to 0:100) to give (R)-3-tert-butoxycarbonylamino-4-(3′-chloro-biphenyl-4-yl)-2-methoxy-butyric acid methyl ester (500 mg). HPLC retention time=1.20, 1.25 minutes (condition B): MS (m+1-Boc)=334. 1H-NMR (400 MHz, CDCl3) δ ppm 1.37, 1.41 (s, 9 H), 2.72-3.03 (m, 2 H), 3.43, 3.71 (s, 3H), 3.63-3.82 (m, 1 H), 4.27-4.41 (m, 1 H), 4.68-5.04 (m, 1 H), 7.28-7.40 (m, 4 H), 7.41-7.61 (m, 4 H).

Workup

  1. stirringstirred for 3 days
  2. filtrationThe reaction mixture is filtered through celite pad
  3. washthe filtrate is washed with brine
  4. dry with materialThe organic layer is dried over MgSO4
  5. concentrationconcentrated
  6. customThe residue is purified by flash column chromatography (silica gel, eluent; heptane/EtOAc=100:0 to 0:100)

Sources & evidence

ORD record
ord-2c62a36d019b4e72842f241d8be42d18
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

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