Formic Acid → HCID 90041622, compound

HRID 929217Notes

Reaction equation

HRID 929217 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[N:26](COCC[Si](C)(C)C)[C:25]([O:35][CH:36]3[CH:40]4[O:41][CH2:42][C@H:43]([OH:44])[CH:39]4[O:38][CH2:37]3)=[N:24][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[C:15]=2[O:22][CH3:23])=[CH:10][CH:9]=1.C(O)=O.OS([O-])(=O)=O.[K+].[OH-].[Na+].Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:26][C:25]([O:35][CH:36]3[CH:40]4[O:41][CH2:42][C@H:43]([OH:44])[CH:39]4[O:38][CH2:37]3)=[N:24][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[C:15]=2[O:22][CH3:23])=[CH:10][CH:9]=1

Participants

7

Reactant 5

HCID 284Formic AcidHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516920Potassium bisulfateHCID 90042306HCID 90042306, compound

Product 1

HCID 90041622HCID 90041622, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

Combined (3S)-6-[6-chloro-5-[4-(3,5-difluoro-2-methoxy-phenyl)phenyl]-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexa-hydrofuro[3,2-b]furan-3-ol (36.8 mg, 0.057 mmol), formic acid (0.6 ml, 15.6 mmol), and saturated aqueous KHSO4 (0.05 ml) in a flask. The yellow solution was heated to 40° C. with stirring. After 22 hours, the reaction mixture was cooled to room temperature before being cooled to 0° C. in an ice bath. Then 5N NaOH (3 ml) was added to the reaction mixture and the mixture was allowed to warm to room temperature. The reaction mixture was diluted with THF (2.0 ml) to give a hazy mixture. After 20 minutes, 2 N aqueous HCl (1.1 mL) was added. The reaction mixture was partitioned between EtOAc (35 ml) and water (20 ml), then the organic phase was washed with brine (1×10 ml), dried over MgSO4, filtered, and evaporated under reduced pressure to a give the product as a solid. LC-MS: calculated for C25H20ClF2N3O5 515.11 observed m/e: 516.10 (M+H)+ (Rt 1.22/2 min)

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. temperaturebefore being cooled to 0° C. in an ice bath
  3. temperatureto warm to room temperature
  4. customto give a hazy mixture
  5. waitAfter 20 minutes
  6. customThe reaction mixture was partitioned between EtOAc (35 ml) and water (20 ml)
  7. washthe organic phase was washed with brine (1×10 ml)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated under reduced pressure to

Sources & evidence

ORD record
ord-a24040d0a84046bf962ac571433e8d6b
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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