Trifluoromethanesulfonic acid, lithium salt → (R)-{3-[7-fluoro-1-(2-fluoro-ethyl)-2-oxo-2,3-dihydro-1H-indol-5-ylamino]-2-hydroxy-propyl}-carbamic acid tert-butyl ester

HRID 2114888Notes

Reaction equation

HRID 2114888 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[N:7]([CH2:12][CH2:13][F:14])[C:6](=[O:15])[CH2:5]2.[C:16]([O:20][C:21](=[O:27])[NH:22][CH2:23][C@H:24]1[CH2:26][O:25]1)([CH3:19])([CH3:18])[CH3:17].FC(F)(F)S([O-])(=O)=O.[Li+]>C(#N)C.C(OCC)(=O)C>[C:16]([O:20][C:21](=[O:27])[NH:22][CH2:23][C@H:24]([OH:25])[CH2:26][NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[N:7]([CH2:12][CH2:13][F:14])[C:6](=[O:15])[CH2:5]2)([CH3:18])([CH3:17])[CH3:19]

Participants

6

Reactant 3

HCID 3664839Trifluoromethanesulfonic acid, lithium saltHCID 10080852(S)-N-Boc-2,3-epoxypropylamineHCID 739475815-Amino-7-fluoro-1-(2-fluoro-ethyl)-1,3-dihydro-indol-2-one

Product 1

HCID 73950634(R)-{3-[7-fluoro-1-(2-fluoro-ethyl)-2-oxo-2,3-dihydro-1H-indol-5-ylamino]-2-hydroxy-propyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Amino-7-fluoro-1-(2-fluoro-ethyl)-1,3-dihydro-indol-2-one (0.39 g, 1.84 mmol), (S)-oxiranylmethyl-carbamic acid tert-butyl ester (0.319 g, 1.84 mmol) and lithium trifluoromethanesulfonate (0.283 g, 1.84 mmol) in acetonitrile (4 ml) are heated at 90° C. for 6 hours. The reaction mixture is diluted with ethyl acetate, washed with water and brine, dried (Na2SO4) and evaporated. Final purification by flash chromatography (70% Ethyl acetate/hexane) gives the title compound as a yellow-brown foamy solid. HPLC r.t. 3.92 min; MS for C18H25F2N3O4 m/z 386.1 (M+H)+.

Workup

  1. washwashed with water and brine
  2. dry with materialdried (Na2SO4)
  3. customevaporated
  4. customFinal purification by flash chromatography (70% Ethyl acetate/hexane)

Sources & evidence

ORD record
ord-59c9be451e3f455c9386be310f4de87b
Source dataset
uspto-grants-2008_10
Patent number
US07435751B2

Reaction notes

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