Sodium Hydroxide → 1-{4-[2-(2-Cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile

HRID 858599Notes

Reaction equation

HRID 858599 reaction equation
[CH:1]1([C:6]([OH:31])([CH2:21][C:22]2[O:23]C(C)(C)[O:25][C:26](=O)[CH:27]=2)[CH2:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3([C:18]#[N:19])[CH2:17][CH2:16]3)=[C:11]([F:20])[CH:10]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+]>>[CH:1]1([C:6]2([CH2:7][CH2:8][C:9]3[CH:14]=[CH:13][C:12]([C:15]4([C:18]#[N:19])[CH2:16][CH2:17]4)=[C:11]([F:20])[CH:10]=3)[CH2:21][C:22](=[O:23])[CH2:27][C:26](=[O:25])[O:31]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 14798Sodium HydroxideHCID 587625831-{4-[3-Cyclopentyl-4-(2,2-dimethyl-6-oxo-6H-[1,3]dioxin-4-yl)-3-hydroxy-butyl]-2-fluoro-phenyl}-cyclopropanecarbonitrile

Product 1

HCID 587627061-{4-[2-(2-Cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopropanecarbonitrileYield 47.3%

Procedure

A solution of 1-{4-[3-Cyclopentyl-4-(2,2-dimethyl-6-oxo-6H-[1,3]dioxin-4-yl)-3-hydroxy-butyl]2-fluoro-phenyl}-cyclopropanecarbonitrile (0.9 g, 2.1 mmol) from Step 6 below in NaOH (0.3 M in MeOH, 21 mL, 6.3 mmol) was stirred at room temperature for 3 hours. The reaction was then quenched with 100 mL saturated NH4Cl and 5 mL 1 N HCl. To this solution was added 100 mL CH2Cl2 and the layers were separated. The aqueous layer was extracted with 2×100 mL CH2Cl2 and the organic layers were combined. After drying the organic with MgSO4, and filtering to remove the solids, the solvent was removed by rotary evaporation. The remaining oil was purified by flash chromatography to yield the desired product (0.367 g, 47%).

Workup

  1. customThe reaction was then quenched with 100 mL saturated NH4Cl and 5 mL 1 N HCl
  2. additionTo this solution was added 100 mL CH2Cl2
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with 2×100 mL CH2Cl2
  5. dry with materialAfter drying the organic with MgSO4
  6. filtrationfiltering
  7. customto remove the solids
  8. customthe solvent was removed by rotary evaporation
  9. customThe remaining oil was purified by flash chromatography

Sources & evidence

ORD record
ord-cf309bdc4a0741c7ab357cee2c65d7f0
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Reaction notes

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