Sodium hydride → (rac)-tert-Butyl 2-(4-(4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yloxy)acetate

HRID 714105Notes

Reaction equation

HRID 714105 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]3[CH2:17][CH2:16][CH:15]([OH:18])[C:11]=3[CH:12]=[N:13][CH:14]=2)=[CH:5][CH:4]=1.[H-].[Na+].Br[CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].OP([O-])(O)=O.[K+]>CN(C=O)C>[F:20][C:2]([F:1])([F:19])[C:3]1[CH:4]=[CH:5][C:6]([C:9]2[C:10]3[CH2:17][CH2:16][CH:15]([O:18][CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:11]=3[CH:12]=[N:13][CH:14]=2)=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 516951Monobasic potassium phosphateHCID 71811532(rac)-4-(4-(Trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-ol

Product 1

HCID 71811491(rac)-tert-Butyl 2-(4-(4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yloxy)acetateYield 70.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A cooled (0° C.) solution of (rac)-4-(4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-ol (example 83) (400 mg, 1.43 mmol) in DMF (4 mL) was treated with NaH (55% in oil, 100 mg, 2.29 mmol) and after ½ h with tert-butyl 2-bromoacetate (201 μL, 1.36 mmol) in DMF (4 mL). After warming up to room temperature overnight, the reaction mixture was poured on aq. 10% KH2PO4 solution followed by extraction with Et2O (3×). The organic phases were washed once with aq. 10% NaCl solution. The combined organic phases were dried (Na2SO4), filtered and purified by flash chromatography (50 g SiO2, Telos-cartridge, 2% 2-propanol in CH2Cl2) to give the title compound (375 mg, 53%) as dark brown oil. MS: 394.2 (M+H+).

Workup

  1. extractionfollowed by extraction with Et2O (3×)
  2. washThe organic phases were washed once with aq. 10% NaCl solution
  3. dry with materialThe combined organic phases were dried (Na2SO4)
  4. filtrationfiltered
  5. custompurified by flash chromatography (50 g SiO2, Telos-cartridge, 2% 2-propanol in CH2Cl2)

Sources & evidence

ORD record
ord-a2dfb925d9e74ebb913f4229537fc2c3
Source dataset
uspto-grants-2015_11
Patent number
US09187429B2

Reaction notes

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