Sodium Hydroxide → {5-tert-Butyl-2-[2-(2-hydroxy-ethoxy)-pyridin-4-yl]-2H-pyrazol-3-yl}-carbamic acid 2,2,2-trichloro-ethyl ester

HRID 711189Notes

Reaction equation

HRID 711189 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([O:13][CH2:14][CH2:15][OH:16])[CH:8]=2)[N:5]=[C:4]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:3]=1.[OH-].[Na+].Cl[C:24]([O:26][CH2:27][C:28]([Cl:31])([Cl:30])[Cl:29])=[O:25]>CCOC(C)=O>[Cl:29][C:28]([Cl:31])([Cl:30])[CH2:27][O:26][C:24](=[O:25])[NH:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([O:13][CH2:14][CH2:15][OH:16])[CH:8]=2)[N:5]=[C:4]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 870632,2,2-Trichloroethyl chloroformate3×HCID 1177296752-[4-(5-Amino-3-tert-butyl-pyrazol-1-yl)-pyridin-2-yloxy]-ethanol

Product 1

HCID 117729672{5-tert-Butyl-2-[2-(2-hydroxy-ethoxy)-pyridin-4-yl]-2H-pyrazol-3-yl}-carbamic acid 2,2,2-trichloro-ethyl esterYield 33%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of Intermediate 67c (139 mg, 0.50 mmol) in EtOAc (5 mL) and 1M NaOH solution (1.26 mL, 1.26 mmol) was added 2,2,2-trichloroethyl chloroformate (117 mg, 76 μL, 0.55 mmol) and the reaction was stirred at RT. After 1 h, a further 1.1 eq of 2,2,2-trichloroethyl chloroformate was added, stirred for an additional 1 h, then a further 2.2 eq. of 2,2,2-trichloroethyl chloroformate added. After stirring for an additional 2 h, the reaction was partitioned between H2O and EtOAc. The organic layer was separated, and the aqueous layer extracted with EtOAc. The combined organics were dried over MgSO4, concentrated in vacuo and subjected to FCC, eluting with 0-50% EtOAc/cyclohexane, and triturated with Et2O to afford the title compound (74 mg, 33%). LCMS (Method 3) Rt 3.93 min, 451.1, 453 [MH+].

Workup

  1. stirringstirred for an additional 1 h
  2. stirringAfter stirring for an additional 2 h
  3. customthe reaction was partitioned between H2O and EtOAc
  4. customThe organic layer was separated
  5. extractionthe aqueous layer extracted with EtOAc
  6. dry with materialThe combined organics were dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. washeluting with 0-50% EtOAc/cyclohexane
  9. customtriturated with Et2O

Sources & evidence

ORD record
ord-2a6095709f524ddb940ce5afec7f41f8
Source dataset
uspto-grants-2015_11
Patent number
US09181242B2

Reaction notes

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