Ethyl Acetate → HCID 59164846, compound

HRID 2264800Notes

Reaction equation

HRID 2264800 reaction equation
[NH2:1][C:2]([C@@H:4]1[CH2:8][CH2:7][C@H:6]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[N:5]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:3].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[F:37].C(OCC)(=O)C>C(#N)C.O>[NH2:1][C:2]([C@@H:4]1[CH2:8][CH2:7][C@H:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[F:37])=[CH:11][CH:10]=2)[N:5]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:3]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 67968alpha-Bromo-o-fluorotolueneHCID 59164822HCID 59164822, compound

Product 1

HCID 59164846HCID 59164846, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 1,1-dimethylethyl (2S,5R)-2-(aminocarbonyl)-5-(4-hydroxyphenyl)-1-pyrrolidinecarboxylate (D13, 45 mg, 0.146 mmol) and potassium carbonate (30 mg, 0.217 mmol) in acetonitrile (2 ml) was added 1-(bromomethyl)-2-fluorobenzene (30 μl, 0.220 mmol). The mixture was stirred overnight at room temperature. Then ethyl acetate and water were added. The organic phase was then washed with brine, dried (Na2SO4), filtered and evaporated. The crude material was purified by chromatography on silica gel using cyclohexane/ethyl acetate (7:3 to 6:4) to afford the title compound (51 mg, 85%); Rt (HPLC): 5.56 min; Rf (cyclohexane:ethyl acetate=1:1): 0.28; 1H-NMR (300 MHz, CDCl3) δ (ppm): 7.56-7.48 (m, 1H); 7.37-7.28 (m, 1H), 7.24-7.06 (m, 5H); 6.93 (d, 2H); 5.45-5.37 (br. s, 1H); 5.15 (s, 2H); 4.73-4.60 (m, 1H); 4.53-4.45 (m, 1H); 2.58-2.48 (m, 1H); 2.34-2.25 (m, 1H); 2.09-1.93 (m, 2H); 1.28-1.13 (br. s, 9H).

Workup

  1. washThe organic phase was then washed with brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude material was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-2bf1c4efae8f492f84055f845cbcbec3
Source dataset
uspto-grants-2010_12
Patent number
US07855218B2

Reaction notes

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