Acetic Acid → (7R,7aR)-2-chloro-4-(7-hydroxy-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile

HRID 501609Notes

Reaction equation

HRID 501609 reaction equation
[Si]([O:8][C@H:9]1[C@:16]2([CH3:17])[N:12]([C:13](=[O:28])[N:14]([C:18]3[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[C:20]([Cl:26])[C:19]=3[CH3:27])[CH2:15]2)[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.C(O)(=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:26][C:20]1[C:19]([CH3:27])=[C:18]([N:14]2[CH2:15][C@:16]3([CH3:17])[C@H:9]([OH:8])[CH2:10][CH2:11][N:12]3[C:13]2=[O:28])[CH:25]=[CH:24][C:21]=1[C:22]#[N:23]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 2724141Tetrabutylammonium Fluoride4×HCID 59754267(7R,7aR)-4-[7-(tert-Butyldimethylsilanyloxy)-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methyl-benzonitrile

Product 1

HCID 59754258(7R,7aR)-2-chloro-4-(7-hydroxy-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrileYield 89.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (7R,7aR)-4-[7-(tert-Butyldimethylsilanyloxy)-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile (58E) (17 mg, 0.04 mmol) in THF (2 mL) was added acetic acid (100 □L) and a 1 M solution of TBAF in THF (122 □L, 0.12 mmol). After stirring at rt for 11 h, additional TBAF solution was added (100 □L), and after stirring for another 6 h, 200 □L TBAF solution was added. The reaction was stirred overnight, then 100 □L TBAF was added and the reaction stirred an additional 1.5 h. The reaction was then quenched with saturated aqueous NH4Cl and extracted with EtOAC. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated under reduced pressure. The resulting residue was purified via preparative HPLC (Luna C-18, 100×21.2 mm, eluting with 40-100% solvent B (A=90% H2O-10% MeOH-0.1% TFA and B=10% H2O-90% MeOH-0.1% TFA) over 10 min; Flow rate at 20 mL/min; UV detection at 220 nm) to provide the title compound (11 mg). LC/MS m/z 306 [M+H]+.

Workup

  1. stirringafter stirring for another 6 h
  2. stirringThe reaction was stirred overnight
  3. stirringthe reaction stirred an additional 1.5 h
  4. customThe reaction was then quenched with saturated aqueous NH4Cl
  5. extractionextracted with EtOAC
  6. washThe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified via preparative HPLC (Luna C-18, 100×21.2 mm
  11. washeluting with 40-100% solvent B (A=90% H2O-10% MeOH-0.1% TFA and B=10% H2O-90% MeOH-0.1% TFA) over 10 min

Sources & evidence

ORD record
ord-7c9ddb3556a4458594efb51f36a1803a
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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