Hydrochloric Acid → HCID 86719436, compound

HRID 2278694Notes

Reaction equation

HRID 2278694 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([N:22]3[C@@H:26]([CH2:27][C:28]([O:30]CC)=[O:29])[C@H:25]([CH3:33])[C:24]([C:34]([F:37])([F:36])[F:35])=[N:23]3)=[CH:18][CH:17]=2)[CH2:11][CH2:10]1.C(Cl)(=O)C.Cl.FC1C=CC(OC)=CC=1N1CCC(OC2C=CC(N3[C@@H](CC(O)=O)[C@H](C)C(C(F)(F)F)=N3)=CC=2)CC1.B(Br)(Br)Br>CCO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[CH:17]=[CH:18][C:19]([N:22]3[C@@H:26]([CH2:27][C:28]([OH:30])=[O:29])[C@H:25]([CH3:33])[C:24]([C:34]([F:35])([F:36])[F:37])=[N:23]3)=[CH:20][CH:21]=2)[CH2:11][CH2:10]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 25134Boron tribromideHCID 77845055HCID 77845055, compoundHCID 86719437HCID 86719437, compound

Product 1

HCID 86719436HCID 86719436, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Ethyl 2-((4S,5S)-1-(4-((1-(2-fluoro-5-hydroxyphenyl)piperidin-4-yl)oxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetate: To a solution of EtOH (0.86 mL) was added acetyl chloride (0.18 mL, 2.6 mmol) to generate anhydrous HCl. After addition, the mixture was warmed to room temp, and 2-((4S,5S)-1-(4-((1-(2-fluoro-5-methoxyphenyl)piperidin-4-yl)oxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetic acid (Example 1, 0.044 g, 0.086 mmol) was added. The mixture was stirred at rt for 1.5 h. The reaction mixture was evaporated to dryness. The residue was dissolved in CH2Cl2 (0.6 mL) and was cooled to −78° C., and BBr3 (0.8 mL, 8.46 mmol) was added. The reaction mixture was stirred for 2 h, and was warmed to −40° C. overnight. The reaction solution was poured over ice and, after 30 min agitation, the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, filtered and evaporated to give 85 mg of a yellow oil that was purified via silica chromatography to give 25 mg of desired product as a clear oil. Anal. Calc'd for C26H29F4N3O4: 523.21, LCMS obs. [M+H]=524.1.

Workup

  1. additionAfter addition
  2. customThe reaction mixture was evaporated to dryness
  3. dissolutionThe residue was dissolved in CH2Cl2 (0.6 mL)
  4. temperaturewas cooled to −78° C.
  5. stirringThe reaction mixture was stirred for 2 h
  6. temperaturewas warmed to −40° C. overnight
  7. additionThe reaction solution was poured over ice and, after 30 min agitation
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. customevaporated

Sources & evidence

ORD record
ord-fd47286168c343748d9b8263bdaea120
Source dataset
uspto-grants-2015_09
Patent number
US09133163B2

Reaction notes

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