HCID 140533337, compound → 1-Benzyl 2-methyl (2R)-2-[(3S)-3-{[(S)-tert-butylsulfinyl]amino}-3-(3,5-difluorophenyl)propyl]pyrrolidine-1,2-dicarboxylate

HRID 1864911Notes

Reaction equation

HRID 1864911 reaction equation
[C:1]([S@@:5](/[N:7]=[CH:8]/[CH2:9][CH2:10][C@@:11]1([C:26]([O:28][CH3:29])=[O:27])[CH2:15][CH2:14][CH2:13][N:12]1[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])=[O:6])([CH3:4])([CH3:3])[CH3:2].[F:30][C:31]1[CH:32]=[C:33]([Mg]Br)[CH:34]=[C:35]([F:37])[CH:36]=1>C1(C)C=CC=CC=1.C1COCC1>[C:1]([S@@:5]([NH:7][C@H:8]([C:33]1[CH:32]=[C:31]([F:30])[CH:36]=[C:35]([F:37])[CH:34]=1)[CH2:9][CH2:10][C@@:11]1([C:26]([O:28][CH3:29])=[O:27])[CH2:15][CH2:14][CH2:13][N:12]1[C:16]([O:18][CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)=[O:17])=[O:6])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 140533337HCID 140533337, compoundHCID 178505930HCID 178505930, compound

Product 1

HCID 866257451-Benzyl 2-methyl (2R)-2-[(3S)-3-{[(S)-tert-butylsulfinyl]amino}-3-(3,5-difluorophenyl)propyl]pyrrolidine-1,2-dicarboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To a stirred solution of 1-benzyl 2-methyl (2R)-2-((3E)-3-{[(S)-tert-butylsulfinyl]imino}propyl)pyrrolidine-1,2-dicarboxylate from Step B (1.56 g, 3.70 mmol) in toluene (30 mL) at −78° C. was added 3,5-difluorophenylmagnesium bromide (14.8 mL of a 0.5 M solution in THF, 7.41 mmol) dropwise. The reaction mixture was stirred for 30 min at −78° C., 3.5 h at −10° C., and then at ambient temperature for 1.5 h. The mixture was quenched with saturated aqueous NH4Cl (50 mL) and extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc-95:5 to 0:100, to give the title compound. MS: m/z=537 (M+1).

Workup

  1. waitat ambient temperature for 1.5 h
  2. customThe mixture was quenched with saturated aqueous NH4Cl (50 mL)
  3. extractionextracted with EtOAc (3×30 mL)
  4. washThe combined organic layers were washed with brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with a gradient of hexane

Sources & evidence

ORD record
ord-b66509053af6445ab9a58504cb1f1f4d
Source dataset
uspto-grants-2009_12
Patent number
US07625901B2

Reaction notes

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