Formic Acid → HCID 68282650, compound

HRID 929144Notes

Reaction equation

HRID 929144 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14]=[C:15]([O:25][C@H:26]4[C@H:30]5[O:31][CH2:32][C@@H:33]([OH:34])[C@H:29]5[O:28][CH2:27]4)[N:16](COCC[Si](C)(C)C)[C:11]3=[CH:10][C:9]=2[Cl:35])=[CH:4][CH:3]=1.C(O)=O.OS([O-])(=O)=O.[K+].[OH-].[Na+].Cl>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14]=[C:15]([O:25][C@H:26]4[C@H:30]5[O:31][CH2:32][C@@H:33]([OH:34])[C@H:29]5[O:28][CH2:27]4)[NH:16][C:11]3=[CH:10][C:9]=2[Cl:35])=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516920Potassium bisulfateHCID 86684749HCID 86684749, compound

Product 1

HCID 68282650HCID 68282650, compound

Procedure

A flask was charged with (3R,3aR,6R,6aR)-6-[5-(4-bromophenyl)-6-chloro-1-(2-trimethylsilylethoxy-methyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (270.1 mg, 0.463 mmol), formic acid (1.5 ml, 39.1 mmol), and saturated aqueous KHSO4 (0.15 ml). The reaction mixture was stirred at room temperature for 16 h, then at 40° C. for 23 h. The reaction mixture was cooled in an ice bath. The pH of the reaction mixture was adjusted to 14 through the addition of 5 N aqueous NaOH (8.0 ml, 40 mmol). The reaction mixture was allowed to warm to room temperature. After 10 min, the pH of the reaction mixture was adjusted to 8 through the addition of 2N aqueous HCl. The reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The organic layers were combined, washed with brine, dried over Na2SO4, filtered, evaporated under reduced pressure, and lyophilized from ethanol and benzene to give the title compound as a yellow solid, which was used without further purification. LC-MS: calculated for C18H15BrClN3O4 450.99, 452.99 observed m/e: 452.05, 454.02 (M+H)+ (Rt 1.15/2 min).

Workup

  1. waitat 40° C. for 23 h
  2. temperatureThe reaction mixture was cooled in an ice bath
  3. temperatureto warm to room temperature
  4. waitAfter 10 min
  5. customThe reaction mixture was partitioned between EtOAc and water
  6. extractionThe aqueous layer was extracted with EtOAc
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-9e1baa4810544478824e8e6dfd41b92e
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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