1,8-Diazabicyclo(5.4.0)undec-7-ene → (7R,7aR)-4-[7-(tert-Butyldimethylsilanyloxy)-7a-methyl-1,3-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile

HRID 751127Notes

Reaction equation

HRID 751127 reaction equation
CO[C:3]([C@@:5]1([CH3:25])[C@H:9]([O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])[CH2:8][CH2:7][N:6]1[C:18](OC(C)(C)C)=[O:19])=[O:4].CCN(C(C)C)C(C)C.[Cl:35][C:36]1[C:43]([CH3:44])=[C:42]([N:45]=C=O)[CH:41]=[CH:40][C:37]=1[C:38]#[N:39].C1CCN2C(=NCCC2)CC1>C(Cl)Cl.C(O)(C(F)(F)F)=O>[Si:11]([O:10][C@H:9]1[C@@:5]2([CH3:25])[N:6]([C:18](=[O:19])[N:45]([C:42]3[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[C:36]([Cl:35])[C:43]=3[CH3:44])[C:3]2=[O:4])[CH2:7][CH2:8]1)([C:14]([CH3:15])([CH3:17])[CH3:16])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 81531DiisopropylethylamineHCID 167318492-Chloro-4-isocyanato-3-methylbenzonitrileHCID 68456372(2R,3R)-3-(tert-Butyldimethylsilanyloxy)-2-methylpyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester-2-methyl ester

Product 1

HCID 59754338(7R,7aR)-4-[7-(tert-Butyldimethylsilanyloxy)-7a-methyl-1,3-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrileYield 88.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of (2R,3R)-3-(tert-Butyldimethylsilanyloxy)-2-methyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester-2-methyl ester (60A) (52 mg, 0.14 mmol) in CH2Cl2 (1.5 mL) and TFA (0.5 mL) was stirred at rt for 2 h. The reaction was concentrated under reduced pressure and dried under vacuum. The residue was dissolved in CH2Cl2 (1.5 mL) and Hunig's base (60 μL, 0.35 mmol) was added. After stirring at rt for 10 min, 2-chloro-4-isocyanato-3-methylbenzonitrile (34 mg, 0.18 mmol) was added and the reaction was stirred at rt overnight. The reaction was treated with DBU (40 μL, 0.27 mmol) and was stirred for 4 h at rt then concentrated under reduced pressure. The residue was purified via chromatography (silica gel) eluting with 30% EtOAc in hexane to provide the title compound (54 mg). LC/MS m/z 434 [M+H]+.

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customdried under vacuum
  3. dissolutionThe residue was dissolved in CH2Cl2 (1.5 mL)
  4. stirringthe reaction was stirred at rt overnight
  5. stirringwas stirred for 4 h at rt
  6. concentrationthen concentrated under reduced pressure
  7. customThe residue was purified via chromatography (silica gel)
  8. washeluting with 30% EtOAc in hexane

Sources & evidence

ORD record
ord-8a0b066582194b409d68a7d70ca36d9c
Source dataset
uspto-grants-2008_07
Patent number
US07405234B2

Reaction notes

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