4-Nitrophenol → (7S,7aS)-2-Chloro-4-(7-hydroxy-1,3-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile

HRID 501597Notes

Reaction equation

HRID 501597 reaction equation
[Cl:1][C:2]1[C:3]([CH3:22])=[C:4]([NH:10][C:11]([N:13]2[CH2:17][CH2:16][C@H:15]([OH:18])[C@H:14]2[C:19](O)=[O:20])=[O:12])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].C1CCC(N=C=NC2CCCCC2)CC1.C1C([N+]([O-])=O)=CC=C(O)C=1>C(#N)C>[Cl:1][C:2]1[C:3]([CH3:22])=[C:4]([N:10]2[C:19](=[O:20])[C@@H:14]3[C@@H:15]([OH:18])[CH2:16][CH2:17][N:13]3[C:11]2=[O:12])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Participants

5

Reactant 3

HCID 9804-NitrophenolHCID 10868DicyclohexylcarbodiimideHCID 59754294(2S,3S)-1-(3-Chloro-4-cyano-2-methylphenylcarbamoyl)-3-hydroxy-pyrrolidine-2-carboxylic acid

Product 1

HCID 59754231(7S,7aS)-2-Chloro-4-(7-hydroxy-1,3-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrileYield 61%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of acid 54B (210 mg, 0.649 mmol) in 15 mL of acetonitrile at rt was added DCC (134 mg, 0.649 mmol) followed by p-nitrophenol (180 mg, 1.30 mmol). The suspension was refluxed for 1 h, cooled to rt and filtered. The filtrate was concentrated under reduced pressure and the residue dissolved in EtOAc, washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, EtOAc/hexanes, 75:25) to afford the title compound (121 mg) as a white foam. 1H NMR (CD3OD) 1.94-2.05 (m, 1H), 2.18, 2.22 (s, 3H), 2.24-2.33 (m, 1H), 3.34-3.40 (m, 1H), 3.67-3.75 (m, 1H), 4.08, 4.16 (d, J=6.05, 1H), 4.35, 4.42 (m, 1H), 7.33, 7.38 (d, J=8.25, 1H), 7.70 (m, 1H); 13C NMR (CD3OD) 15.90, 16.11, 36.95, 37.05, 44.88, 45.06, 70.91, 70.94, 72.46, 72.90, 115.19, 115.53, 116.60, 116.66, 129.30, 129.46, 132.74, 133.03, 137.41, 137.61, 138.08, 138.37, 138.42, 138.53, 159.69, 159.97, 172.10, 172.43; HPLC a) column: Phenomenex LUNA C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA; 1 min hold, 4 mL/min UV detection at 220 nm, 2.32 min retention time; HPLC b) column: Shimadzu Shim-Pack VP-ODS C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold; 4 mL/min, UV detection at 220 nm, 2.15 min retention time (100%); HPLC c) column: Daicel Chiralcel OD 4.6×250 mm, Isocratic 25% Isopropanol/Hexanes, 30 min, 1 mL/min, UV detection at 220 nm, 17.65 min retention time (99%); MS (ES) m/z 306 [M+H]+.

Workup

  1. temperatureThe suspension was refluxed for 1 h
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutionthe residue dissolved in EtOAc
  5. washwashed with water and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (silica gel, EtOAc/hexanes, 75:25)

Sources & evidence

ORD record
ord-d6aa313285f84909a2b70df919a5477e
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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