Trifluoroacetic acid → HCID 86638156, compound

HRID 423406Notes

Reaction equation

HRID 423406 reaction equation
B.C1COCC1.[Br:7][C:8]1[CH:9]=[CH:10][C:11]([N:14]2[CH2:18][CH2:17][C@H:16]([NH:19][C:20](=O)[CH:21]([F:23])[F:22])[CH2:15]2)=[N:12][CH:13]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].FC(F)(F)C(O)=O>O1CCCC1.ClCCl>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([N:14]2[CH2:18][CH2:17][C@H:16]([NH:19][CH2:20][CH:21]([F:23])[F:22])[CH2:15]2)=[N:12][CH:13]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 2723981Borane;tetrahydrofuranHCID 5049666Sodium triacetoxyborohydrideHCID 66673305HCID 66673305, compound

Product 1

HCID 86638156HCID 86638156, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Add via syringe 1M BH3-THF (78 mL, 78 mmol) to a solution of N—[(S)-1-(5-bromo-pyridin-2-yl)-pyrrolidin-3-yl]-2,2-difluoro-acetamide (8.3 g, 25 mmol) in tetrahydrofuran (65 mL) and heat the mixture at reflux overnight. Cool the reaction to 0° C. and slowly quench with 5N NaOH until no gas evolution is observed. Concentrate the material in vacuo to remove THF. Dilute the residue with water (150 mL) and extract with CH2Cl2 (3×150 mL). Dry the combined organics over Na2SO4, filter, and concentrate to dryness. Add sodium triacetoxyborohydride (35.4 g, 167 mmol) to the residue in dichloromethane (75 mL). Add dropwise trifluoroacetic acid (150 mL) with vigorous stirring. After 10 min concentrate the mixture in vacuo and dilute with CH2Cl2 (150 mL). Cool the mixture in an ice bath and slowly basify to pH 9 with 5N NaOH. Stir the basic mixture overnight. Dilute the mixture with water (200 mL) and extract with CH2Cl2 (3×150 mL). Dry the combined organics over Na2SO4, filter, and concentrate to dryness. Purify by chromatography to afford 6.38 g (85%) of the title compound. MS/ES m/z (79Br) 306.0 [M+H]+.

Workup

  1. temperatureheat the mixture
  2. temperatureat reflux overnight
  3. temperatureCool
  4. customthe reaction to 0° C.
  5. customslowly quench with 5N NaOH until no gas evolution
  6. concentrationConcentrate the material in vacuo
  7. customto remove THF
  8. additionDilute the residue with water (150 mL)
  9. extractionextract with CH2Cl2 (3×150 mL)
  10. dry with materialDry the combined organics over Na2SO4
  11. filtrationfilter
  12. concentrationconcentrate to dryness
  13. concentrationAfter 10 min concentrate the mixture in vacuo
  14. additiondilute with CH2Cl2 (150 mL)
  15. temperatureCool the mixture in an ice bath
  16. additionDilute the mixture with water (200 mL)
  17. extractionextract with CH2Cl2 (3×150 mL)
  18. dry with materialDry the combined organics over Na2SO4
  19. filtrationfilter
  20. concentrationconcentrate to dryness
  21. customPurify by chromatography

Sources & evidence

ORD record
ord-da980f8b526e40a3b957ea0a4aa25f47
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

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