Ethyl Acetate → HCID 59164846, compound

HRID 1691494Notes

Reaction equation

HRID 1691494 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[F:9].[NH2:10][C:11]([C@@H:13]1[CH2:17][CH2:16][C@H:15]([C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=2)[N:14]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[O:12].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C(#N)C.O>[NH2:10][C:11]([C@@H:13]1[CH2:17][CH2:16][C@H:15]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[F:9])=[CH:20][CH:19]=2)[N:14]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[O:12]

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

1-(Bromomethyl)-2-fluorobenzene (30 μl, 0.220 mmol) was added to a solution of 1,1-dimethylethyl (2S,5R)-2-(aminocarbonyl)-5-(4-hydroxyphenyl)-1-pyrrolidinecarboxylate (D9, 45 mg, 0.146 mmol) and potassium carbonate (30 mg, 0.217 mmol) in acetonitrile (2 ml). The mixture was stirred overnight at room temperature. After the reaction was finished, as shown by TLC, 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. additionwere added
  2. washThe organic phase was then washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude material was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-a81b0a9cee86488393c7beb6448ae8ed
Source dataset
uspto-grants-2012_04
Patent number
US08153681B2

Reaction notes

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