Sodium hydride → (rac)-7-((3-Methyloxetan-3-yl)methoxy)-4-(4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridine

HRID 714111Notes

Reaction equation

HRID 714111 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+].I[CH2:24][C:25]1([CH3:29])[CH2:28][O:27][CH2:26]1.OP([O-])(O)=O.[K+]>CN(C=O)C>[CH3:24][C:25]1([CH2:29][O:18][CH:15]2[C:11]3[CH:12]=[N:13][CH:14]=[C:9]([C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:19])[F:20])=[CH:8][CH:7]=4)[C:10]=3[CH2:17][CH2:16]2)[CH2:28][O:27][CH2:26]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516951Monobasic potassium phosphateHCID 137783443-(Iodomethyl)-3-methyloxetaneHCID 71811532(rac)-4-(4-(Trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-ol

Product 1

HCID 71811451(rac)-7-((3-Methyloxetan-3-yl)methoxy)-4-(4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridineYield 29%

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) (75 mg, 0.27 mmol) in DMF (1.4 mL) was treated with NaH (55% in oil, 18.7 mg, 0.43 mmol) and after ½ h with 3-(iodomethyl)-3-methyloxetane (209 mg, 0.59 mmol, synthesized by refluxing 3-(chloromethyl)-3-methyloxetane with 5 eq. sodium iodide in acetone overnight) in DMF (1 mL). After warming up to room temperature over 5 h, 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 (20 g SiO2, Telos-cartridge, 1 to 3% 2-propanol in CH2Cl2) to give the title compound (28 mg, 29%) as brown oil. MS: 364.5 (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 (20 g SiO2, Telos-cartridge, 1 to 3% 2-propanol in CH2Cl2)

Sources & evidence

ORD record
ord-96be935962e049549c0455744645d7d0
Source dataset
uspto-grants-2015_11
Patent number
US09187429B2

Reaction notes

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