Potassium trimethylsilanolate → 3-{(5S,7S)-7-[(6-cyano-1H-benzimidazol-1-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]dec-3-yl}-2,2-dimethylpropanoic acid

HRID 715499Notes

Reaction equation

HRID 715499 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[CH:9][N:8]([CH2:11][C@H:12]3[CH2:30][CH2:29][CH2:28][C@:14]4([O:18][C:17](=[O:19])[N:16]([CH2:20][C:21]([CH3:27])([CH3:26])[C:22]([O:24]C)=[O:23])[CH2:15]4)[CH2:13]3)[C:7]=2[CH:31]=1)#[N:2].C[Si](C)(C)[O-].[K+]>C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[CH:9][N:8]([CH2:11][C@H:12]3[CH2:30][CH2:29][CH2:28][C@:14]4([O:18][C:17](=[O:19])[N:16]([CH2:20][C:21]([CH3:26])([CH3:27])[C:22]([OH:24])=[O:23])[CH2:15]4)[CH2:13]3)[C:7]=2[CH:31]=1)#[N:2]

Participants

4

Reactant 2

HCID 23668039Potassium trimethylsilanolate2×HCID 71136167methyl 3-{(5S,7S)-7-[(6-cyano-1H-benzimidazol-1-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]dec-3-yl}-2,2-dimethylpropanoate

Product 1

HCID 712275233-{(5S,7S)-7-[(6-cyano-1H-benzimidazol-1-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]dec-3-yl}-2,2-dimethylpropanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of methyl 3-{(5S,7S)-7-[(6-cyano-1H-benzimidazol-1-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]dec-3-yl}-2,2-dimethylpropanoate (1.06 g, 2.505 mmol) and potassium trimethylsilanolate (0.482 g, 3.76 mmol) in THF (12.5 mL) was stirred at RT overnight. LCMS showed the reaction was not complete. Additional potassium trimethylsilanolate (0.482 g, 3.76 mmol) was then added, and the reaction was stirred for one additional day. The reaction mixture was then concentrated to a light yellow solid. The solid was washed with a mixture of DCM and Et2O and dried under vacuum to give 3-{(5S,7S)-7-[(6-cyano-1H-benzimidazol-1-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]dec-3-yl}-2,2-dimethylpropanoic acid as a light yellow solid. This product was used in the next step without any further purification. MS (m/z) 411.2 (M+H+).

Workup

  1. stirringthe reaction was stirred for one additional day
  2. concentrationThe reaction mixture was then concentrated to a light yellow solid
  3. washThe solid was washed with a mixture of DCM and Et2O
  4. customdried under vacuum

Sources & evidence

ORD record
ord-a0efcd07451e4389a501ebdffaa98c96
Source dataset
uspto-grants-2015_11
Patent number
US09187464B2

Reaction notes

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