Ethyl Acetate → HCID 59164824, compound

HRID 1441898Notes

Reaction equation

HRID 1441898 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 59164838HCID 59164838, compound

Product 1

HCID 59164824HCID 59164824, compoundYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

1-(Bromomethyl)-2-fluorobenzene (30 μl, 0.244 mmol) was added to a solution of 1,1-dimethylethyl (2S,5S)-2-(aminocarbonyl)-5-(4-hydroxyphenyl)-1-pyrrolidinecarboxylate (D14, 50 mg, 0.163 mmol) and potassium carbonate (34 mg, 0.244 mmol) in acetonitrile (0.5 ml). The mixture was stirred overnight at room temperature. Then ethyl acetate (20 mL) and water (10 mL) were added. The organic phase was dried over Na2SO4, filtered and evaporated under reduced pressure. The crude material was purified by chromatography on silica gel using cyclohexane/ethyl acetate (7:3 to 6:4) to afford the title compound (65 mg, 97%); Rf (cyclohexane:ethyl acetate=7:3): 0.19; MS: (ES/+) m/z: 437 [M+Na+], C23H27FN2O4 requires 414; Rt (HPLC): 5.28 min; 1H NMR (400 MHz, DMSO-d6) δ(ppm): 7.54-7.44 (m, 1H), 7.40-7.27 (m, 2H), 7.24-7.11 (m, 2H), 7.06-6.98 (m, 2H), 6.96-6.79 (m, 3H), 5.10-5.00 (m, 2H), 4.91 and 4.81 (d, d, 1H), 4.29 and 4.24 (d, d, 1H), 2.35-2.18 (m, 1H), 2.17-1.97 (m, 1H), 1.78-1.62 (m, 1H), 1.58-1.43 (m, 1H), 1.28 and 1.03 (s, s, 9H).

Workup

  1. dry with materialThe organic phase was dried over Na2SO4
  2. filtrationfiltered
  3. customevaporated under reduced pressure
  4. customThe crude material was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-1265cb64b9294580a5ab7174f42287f9
Source dataset
uspto-grants-2010_02
Patent number
US07655693B2

Reaction notes

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