Methyl iodide → (R)-2-((tert-butoxycarbonyl)amino)-3-methoxy-3-methylbutanoic acid
Reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][C@H:11]([C:15]([OH:18])([CH3:17])[CH3:16])[C:12]([OH:14])=[O:13])=[O:9])([CH3:6])([CH3:5])[CH3:4].I[CH3:20]>C1COCC1>[C:3]([O:7][C:8]([NH:10][C@H:11]([C:15]([O:18][CH3:20])([CH3:17])[CH3:16])[C:12]([OH:14])=[O:13])=[O:9])([CH3:6])([CH3:4])[CH3:5]Participants
Procedure
To a solution of sodium hydride suspension in mineral oil (60% wt) (3.86 g, 96 mmol) in dry THF (60 mL) were added (R)-2-((tert-butoxycarbonyl)amino)-3-hydroxy-3-methylbutanoic acid (7.5 g, 32.2 mmol) in THF (50 mL) at 0° C. slowly. After stirring for 1 h at room temperature, iodomethane (4.31 ml, 38.6 mmol) was added. The reaction mixture was stirred at room temperature overnight. After quenched with water, the reaction mixture was extracted by ether. The aqueous layers was acidify to pH=3 by adding 6 N HCl, then extracted by EtOAc. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered though Buchner funnel, and concentrated to yield crude (R)-2-((tert-butoxycarbonyl)amino)-3-methoxy-3-methylbutanoic acid (7 g, 28.3 mmol, 88%), which was used in next step reaction without purification. LC/MS (uplc): MH+ 160.1, 0.68 min.
Workup
- stirringThe reaction mixture was stirred at room temperature overnight
- customAfter quenched with water
- extractionthe reaction mixture was extracted by ether
- additionby adding 6 N HCl
- extractionextracted by EtOAc
- washThe organic layer was washed with brine
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered though Buchner funnel
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-5178220deeca4f578a90971b1e371baf
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08546434B2
Reaction notes
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