Potassium Phosphate, Tribasic → HCID 71140780, compound

HRID 629893Notes

Reaction equation

HRID 629893 reaction equation
FC(F)(F)S(O[C:7]1[CH2:8][CH:9]2[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][CH:10]2[CH:21]=1)(=O)=O.C([O-])(=O)C.[K+].Cl[C:30]1[N:35]=[C:34]2[N:36]([CH3:47])[S:37](=[O:46])(=[O:45])[N:38]([CH2:39][CH:40]3[CH2:42][C:41]3([F:44])[F:43])[C:33]2=[CH:32][CH:31]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.O1CCOCC1>[F:44][C:41]1([F:43])[CH2:42][CH:40]1[CH2:39][N:38]1[C:33]2[C:34](=[N:35][C:30]([C:7]3[CH2:8][CH:9]4[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:11][CH:10]4[CH:21]=3)=[CH:31][CH:32]=2)[N:36]([CH3:47])[S:37]1(=[O:45])=[O:46]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 866879055-Chloro-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxideHCID 89303915tert-butyl 5-(((trifluoromethyl)sulfonyl)oxy)-3,3a,6,6a-tetrahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

Product 1

HCID 71140780HCID 71140780, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

tert-Butyl 5-{[(Trifluoromethyl)sulfonyl]oxy}-3,3a,4,6a-tetrahydrocyclo-penta[c]pyrrole-2(1H)-carboxylate (8-2, 1.3 g, 3.64 mmol, 1.0 equiv), bis(pinocolato)diboron (1.0 g, 4.0 mmol, 1.1 equiv), potassium acetate (1.1 g, 10.91 mmol, 3.0 equiv) and PdCl2(dppf) (0.19 g, 0.26 mmol, 0.07 equiv) were added to anhydrous 1,4-dioxane (4.6 mL) and heated to 60° C. After 18 h, the reaction contents were cooled to RT, followed by the subsequent addition of water (0.93 mL), 5-chloro-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro[1,2,5]-thiadiazole[3,4-b]pyridine 2,2-dioxide (23-2, 1.1 g, 3.64 mmol, 1.0 equiv), K3PO4 (1.9 g, 9.09 mmol, 2.5 equiv), (S)-Phos (0.15 g, 0.36 mmol, 0.10 equiv) and palladium(II) acetate (4.1 mg, 0.18 mmol, 0.05 equiv). The resulting mixture was heated to 70° C. for 9 h. Following this duration, LCMS showed consumption of starting material. The contents were then cooled to room temperature, diluted with ethyl acetate (20 mL), filtered through Celite and rinsed with ethyl acetate (3×5 mL) and water (1×5 mL). The filtrate layers were separated and the combined organics were washed with saturated NaHCO3 (10 mL). The combined aqueous layers were then back-extracted with ethyl acetate (3×5 mL). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give a dark orange oil. Purification by normal-phase chromatography (0-50% EtOAc:Hex) afforded 24-1 as a tan solid. MS m/z (M+H): calculated=482.5; observed=482.1.

Workup

  1. customthe reaction contents
  2. temperaturewere cooled to RT
  3. temperatureThe resulting mixture was heated to 70° C. for 9 h
  4. customconsumption of starting material
  5. temperatureThe contents were then cooled to room temperature
  6. additiondiluted with ethyl acetate (20 mL)
  7. filtrationfiltered through Celite
  8. washrinsed with ethyl acetate (3×5 mL) and water (1×5 mL)
  9. customThe filtrate layers were separated
  10. washthe combined organics were washed with saturated NaHCO3 (10 mL)
  11. extractionThe combined aqueous layers were then back-extracted with ethyl acetate (3×5 mL)
  12. dry with materialThe combined organics were dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customto give a dark orange oil
  16. customPurification by normal-phase chromatography (0-50% EtOAc:Hex)

Sources & evidence

ORD record
ord-311d72be03cc477a9da6284cd6f566db
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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