Hydrochloric Acid → (S)-(1-((2-amino-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)methanol

HRID 42998Notes

Reaction equation

HRID 42998 reaction equation
[OH:1][CH2:2][C:3]1[C:4]([C:29]([F:32])([F:31])[F:30])=[N:5][N:6]([CH2:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[CH2:14][C@H:13]([NH:18]C(=O)OCC2C=CC=CC=2)[CH2:12]3)[CH:7]=1.C(O)C.Cl.[H][H]>C(Cl)Cl.O=[Si]=O.[OH-].[Pd+2].[OH-]>[NH2:18][C@@H:13]1[CH2:12][C:11]2[C:15](=[CH:16][CH:17]=[C:9]([CH2:8][N:6]3[CH:7]=[C:3]([CH2:2][OH:1])[C:4]([C:29]([F:32])([F:31])[F:30])=[N:5]3)[CH:10]=2)[CH2:14]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 68364703HCID 68364703, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 67026034(S)-(1-((2-amino-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)methanolYield 70.7%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 6344DichloromethaneSolventHCID 24261SilicaSolvent

Procedure

Palladium hydroxide (20% on carbon, 6.38 mmol, 0.895 g) was wetted in a hydrogenation vessel before addition of (S)-benzyl 5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-ylcarbamate (6.38 mmol, 2.84 g) and ethanol (50 mL) followed by aqueous 5N HCl solution (5.00 mL). The mixture was stirred under 2 bar of hydrogen for 1 hour before diluting with DCM (100 mL) and filtration through a dicalite pad which was then washed with 10% MeOH/DCM (200 mL). Combined organics were concentrated and partitioned between ethylacetate and saturated sodium carbonate solution. The organic layer was concentrated to give a light yellow oil which was purified on silica eluting with 5.5% 2M NH3-MeOH/DCM to give (S)-(1-((2-amino-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)methanol (1.40 g, 70.7%). 1H NMR (400 MHz, CDCl3) δ 2.65 (m, 2H) 3.16 (m, 2H) 3.82 (m, 1H) 4.59 (s, 2H) 5.23 (s, 2H) 7.06 (d, 1H) 7.10 (s, 1H) 7.18 (d, 1H) 7.38 (s, 1H)

Workup

  1. washwas then washed with 10% MeOH/DCM (200 mL)
  2. concentrationCombined organics were concentrated
  3. custompartitioned between ethylacetate and saturated sodium carbonate solution
  4. concentrationThe organic layer was concentrated
  5. customto give a light yellow oil which
  6. customwas purified on silica eluting with 5.5% 2M NH3-MeOH/DCM

Sources & evidence

ORD record
ord-b0a4c21aa1db41358d65ee3a4679e7cd
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

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