Tetrabutylammonium Fluoride → 4-[(1S,7R,7aR)-7-Hydroxy-1-methyl-3-oxohexahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile

HRID 501657Notes

Reaction equation

HRID 501657 reaction equation
[O:1]([C@@H:9]1[C@@H:16]2[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])[C@@H:15]2[CH3:17])[CH2:11][CH2:10]1)[Si](C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[OH:1][C@H:9]1[C@@H:16]2[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])[C@H:15]2[CH3:17])[CH2:11][CH2:10]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 167319934-[(1R,7S,7aR)-7-tert-Butyldimethylsilanoxy-1-methyl-3-oxohexahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrile

Product 1

HCID 167315144-[(1S,7R,7aR)-7-Hydroxy-1-methyl-3-oxohexahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methylbenzonitrileYield 64.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 80G (11 mg, 0.026 mmol) in THF (1 mL) was added TBAF 1.0 M in THF, 0.26 mL). The reaction was stirred at rt for 2 h. The reaction mixture was concentrated and the residue was purified by reverse phase HPLC (Phenomenex Luna 20×100 mm S5 C18, 10 min. grad, 20 mL/min, 20-100% B solvent, A=10% MeOH/water+0.1% TFA, B=90% MeOH/Water+0.1% TFA) to provide the title compound (5.1 mg): HPLC (Phenomenex Luna 5 u C18 4.6×50 mm, linear gradient over 4 min) retention time 2.40 min (100%); Chiral analytical HPLC (ChiralPak AD 4.6×250 mm, 20% IPA/hexane isocratic) retention time 18.6 min (100% ee); MS (ES) m/z 306.1 [M+H]+; HRMS calcd for C15H17ClN3O2 306.1009, Found 306.1010.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was purified by reverse phase HPLC (Phenomenex Luna 20×100 mm S5 C18, 10 min.

Sources & evidence

ORD record
ord-917d88b1b5034142b15d26467021010a
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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