Dichloromethane → (7R,7aS)-2-Chloro-4-(7-hydroxy-7a-methyl-1,3-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile

HRID 501569Notes

Reaction equation

HRID 501569 reaction equation
CO[C:3]([C@:5]1([CH3:18])[C@H:9]([OH:10])[CH2:8][CH2:7][N:6]1[C:11]([O:13]C(C)(C)C)=O)=[O:4].CC[N:21](C(C)C)C(C)C.Cl[C:29]1[C:30](C)=[C:31]([CH2:35][C:36]([NH2:38])=O)C=[CH:33][CH:34]=1.[CH2:40]([Cl:42])Cl>>[Cl:42][C:40]1[C:34]([CH3:33])=[C:29]([N:21]2[C:3](=[O:4])[C@:5]3([CH3:18])[C@H:9]([OH:10])[CH2:8][CH2:7][N:6]3[C:11]2=[O:13])[CH:30]=[CH:31][C:35]=1[C:36]#[N:38]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 59754263(2S,3R)-3-Hydroxy-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 684549373-Chloro-2-methylphenylacetamide

Product 1

HCID 59754251(7R,7aS)-2-Chloro-4-(7-hydroxy-7a-methyl-1,3-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile

Procedure

To a solution of (2S,3R)-3-hydroxy-2-methyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (25A) (87 mg, 0.32 mmol) in CH2Cl2 (1.3 mL) at 0° C. was added Hunig's base (111 mL, 0.64 mmol). After stirring for 15 min, 2-chloro-4-isocyanato-3-methylbenzonitrile (23A) was added, and after an additional 10 min, the ice bath was removed. The reaction was stirred for 2 h and then diluted with water. The layers were separated and the organic layer was washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting solid was purified using preparative HPLC (Luna C-18, 21.2×100 mm, eluting with 40-100% solvent B (A=90% H2O-10% MeOH and B=10% H2O-90% MeOH) over 15 min; Flow rate at 20 mL/min; UV detection at 220 nm) to provide the title compound (67 mg) as a white film; LC/MS m/z 661 [2M+23]+.

Workup

  1. waitafter an additional 10 min
  2. customthe ice bath was removed
  3. stirringThe reaction was stirred for 2 h
  4. additiondiluted with water
  5. customThe layers were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting solid was purified
  11. washeluting with 40-100% solvent B (A=90% H2O-10% MeOH and B=10% H2O-90% MeOH) over 15 min

Sources & evidence

ORD record
ord-c377fea4c2da400ea6b4359104c91393
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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