Methyl iodide → N-Boc-(R)-2-(MethylaMino)butyric acid

HRID 1518771Notes

Reaction equation

HRID 1518771 reaction equation
[NH:1]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@@H:2]([C:6]([OH:8])=[O:7])[CH:3]([CH3:5])C.[CH3:16]I.[H-].[Na+]>C1COCC1.C(OCC)C>[C:12]([O:11][C:9]([N:1]([CH3:16])[C@H:2]([CH2:3][CH3:5])[C:6]([OH:8])=[O:7])=[O:10])([CH3:13])([CH3:14])[CH3:15]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 637605(2R)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoic acid

Product 1

HCID 58615437N-Boc-(R)-2-(MethylaMino)butyric acidYield 100.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-Boc-D-Val-OH (0.678 g, 3.34 mmol) in THF (11.1 mL) at 0° C. was added MeI (2.09 mL, 33.4 mmol, 10.0 equiv). NaH (60%, 1.33 g, 33.4 mmol, 10.0 equiv) was added as a solid to the suspension over a period of 2 hours. After stirring for 12 hours at room temperature, the reaction mixture was diluted with diethyl ether and quenched with water slowly. Aqueous layer was extracted with diethyl ether followed by acidified to pH 3 with 10% citric acid and extraction with ethyl acetate. Combined organic layer was washed with brine, dried with Na2SO4, filtered and concentrated in vacuo to afford compound 3.1a (0.73 g) which was used for the next step without further purification. MS m/z (M+Na) 240.2. 1H NMR (400 MHz, CDCl3) 4.56 and 4.37 (br-s, 1H), 2.83 (br-s, 3H), 2.08-1.92 (m, 1H), 1.85-1.68 (m, 1H), 1.48 (br-s, 9H), 0.96 (t, J=7.38 Hz, 3H).

Workup

  1. customquenched with water slowly
  2. extractionAqueous layer was extracted with diethyl ether
  3. extractionby acidified to pH 3 with 10% citric acid and extraction with ethyl acetate
  4. washCombined organic layer was washed with brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6ad23920d8d74c4a84ede014f6a4ea7a
Source dataset
uspto-grants-2015_07
Patent number
US09072696B2

Reaction notes

Loading…