Hydrochloric Acid → 2-(4-tert-Butylphenyl)-N-{(S)-[1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}acetamide

HRID 877384Notes

Reaction equation

HRID 877384 reaction equation
C([O:3][C:4](=O)[CH2:5][N:6]1[CH:10]=[C:9]([C@H:11]([NH:24][C:25](=[O:37])[CH2:26][C:27]2[CH:32]=[CH:31][C:30]([C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:29][CH:28]=2)[C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[CH:14][N:13]=2)[N:8]=[N:7]1)C.[Li+].[BH4-].Cl.[OH-].[Na+]>C1COCC1>[C:33]([C:30]1[CH:31]=[CH:32][C:27]([CH2:26][C:25]([NH:24][C@@H:11]([C:9]2[N:8]=[N:7][N:6]([CH2:5][CH2:4][OH:3])[CH:10]=2)[C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]([F:22])([F:23])[F:21])=[CH:14][N:13]=2)=[O:37])=[CH:28][CH:29]=1)([CH3:36])([CH3:34])[CH3:35]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 4148881Lithium borohydrideHCID 131732598ethyl(4-{(S)-{[(4-tert-butylphenyl)acetyl]amino}[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)acetate

Product 1

HCID 681568672-(4-tert-Butylphenyl)-N-{(S)-[1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}acetamideYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of ethyl(4-{(S)-{[(4-tert-butylphenyl)acetyl]amino}[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)acetate (0.190 g, 0.356 mmol) in 1.0 ml of anhydrous THF at RT was added 2.0N LiBH4 in THF (0.214 ml, 0.427 mmol). The resulting solution was stirred at room temperature for 16 hours. The reaction mixture was quenched with 1.0N HCl (2.0 ml, 2.000 mmol), stirred for 30 min. and 2.0 N NaOH (2.0 ml, 4.000 mmol) was added. The mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuum. Purification by preparative HPLC (20-90% CH3CN/H2O over 30 min, 0.05% added TFA, C18 column) to afford 0.047 g (27%) of the title compound. ES-MS [M+1]+: 492.3. This intermediate was carried over to the next step without further purification and characterization.

Workup

  1. stirringstirred for 30 min.
  2. extractionThe mixture was extracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuum
  7. customPurification
  8. additionby preparative HPLC (20-90% CH3CN/H2O over 30 min, 0.05% added TFA, C18 column)

Sources & evidence

ORD record
ord-6e874e7bfe3444e68fb520fb78e250f3
Source dataset
uspto-grants-2015_03
Patent number
US08987310B2

Reaction notes

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