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

HRID 2114903Notes

Reaction equation

HRID 2114903 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][CH:13]1[CH2:15][CH2:14]1)[C:6](=[O:16])[CH2:5]2.[C:17]([O:21][C:22](=[O:28])[NH:23][CH2:24][C@H:25]1[CH2:27][O:26]1)([CH3:20])([CH3:19])[CH3:18].FC(F)(F)S([O-])(=O)=O.[Li+]>C(#N)C.C(OCC)(=O)C>[C:17]([O:21][C:22](=[O:28])[NH:23][CH2:24][C@H:25]([OH:26])[CH2:27][NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([F:11])[CH:10]=1)[N:7]([CH2:12][CH:13]1[CH2:15][CH2:14]1)[C:6](=[O:16])[CH2:5]2)([CH3:19])([CH3:18])[CH3:20]

Participants

6

Reactant 3

HCID 3664839Trifluoromethanesulfonic acid, lithium saltHCID 10080852(S)-N-Boc-2,3-epoxypropylamineHCID 692754005-Amino-1-cyclopropylmethyl-7-fluoro-1,3-dihydro-indol-2-one

Product 1

HCID 69270675(R)-[3-(1-cyclopropylmethyl-7-fluoro-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-1-cyclopropylmethyl-7-fluoro-1,3-dihydro-indol-2-one (1.00 g, 4.55 mmol), (S)-oxiranylmethyl-carbamic acid tert-butyl ester (0.79 g, 4.55 mmol) and lithium trifluoromethanesulfonate (0.618 g, 4.55 mmol) in acetonitrile (20 ml) are heated at 90° C. for 16 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 white solid. HPLC r.t. 4.35 min; MS for C20H28FN3O4 m/z 394.1 (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-b52df95fc6314069809253313dfdddca
Source dataset
uspto-grants-2008_10
Patent number
US07435751B2

Reaction notes

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