2,2,2-Trifluoro-1-methoxyethanol → HCID 86706054, compound

HRID 2176219Notes

Reaction equation

HRID 2176219 reaction equation
[CH3:1][O:2][C:3](=[O:9])[C@@H:4]([NH2:8])[CH:5]([CH3:7])[CH3:6].[F:10][C:11]([F:17])([F:16])[CH:12](OC)O>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:1][O:2][C:3](=[O:9])[C@@H:4]([N:8]=[CH:12][C:11]([F:17])([F:16])[F:10])[CH:5]([CH3:7])[CH3:6]

Participants

5

Reactant 2

HCID 98922,2,2-Trifluoro-1-methoxyethanolHCID 94285Valine methyl ester

Product 1

HCID 86706054HCID 86706054, compoundYield 56.7%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 1140TolueneSolvent

Procedure

A solution of (S)-2-amino-3-methyl-butyric acid methyl ester hydrochloride (6.72 g, 40 mmol) in water (50 mL) was partitioned between saturated sodium hydrogen carbonate solution and dichloromethane. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated to afford (S)-2-amino-3-methyl-butyric acid methyl ester (40 mmol). A solution of (S)-2-amino-3-methyl-butyric acid methyl ester (40 mmol), 2,2,2-trifluoro-1-methoxy-ethanol (5.2 g, 3.8 mL, 40 mmol) and 4-toluenesulfonic acid hydrate (100 mg) in toluene (125 mL) was heated at reflux using a Dean-Stark apparatus for 3 h. The reaction mixture was cooled to room temperature and the solvent was evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 10:1 to 5:1 to afford the title compound (4.79 g, 56%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 0.94 (d, J=7.1 Hz, 3H), 0.97 (d, J=7.1 Hz, 3H), 2.32-2.44 (m, 1H), 3.73-3.77 (m, 4H), 7.67 (q, J=3.3 Hz, 1H).

Workup

  1. temperatureat reflux
  2. customfor 3 h
  3. customthe solvent was evaporated
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-9358d25f655c4a72a24e85c94c339ea0
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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