Nitrogen → (4-Cyclopropanesulfonyl-phenyl)-[(tetrahydro-pyran-4-yloxy)]-acetic acid ethyl ester

HRID 524386Notes

Reaction equation

HRID 524386 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[C:5]([C:8]1[CH:13]=[CH:12][C:11]([S:14]([CH:17]2[CH2:19][CH2:18]2)(=[O:16])=[O:15])=[CH:10][CH:9]=1)=[N+]=[N-])[CH3:2].[OH:21][CH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.N#N.O>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:20])[CH:5]([C:8]1[CH:13]=[CH:12][C:11]([S:14]([CH:17]2[CH2:19][CH2:18]2)(=[O:16])=[O:15])=[CH:10][CH:9]=1)[O:21][CH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)[CH3:2]

Participants

6

Reactant 4

HCID 947NitrogenHCID 962WaterHCID 74956Tetrahydro-4H-pyran-4-olHCID 72281714HCID 72281714, compound

Product 1

HCID 59610050(4-Cyclopropanesulfonyl-phenyl)-[(tetrahydro-pyran-4-yloxy)]-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a stirred solution of compound 2-[4-(Cyclopropanesulfonyl)phenyl]-2-diazo acetic acid ethyl ester (11.3 g, 38 mmol) in DCM (110 mL) under argon atmosphere, 4-hydroxy tetrahydropyran (4.36 mL, 45 mmol) was added followed by portion wise addition of rhodium(II)acetate dimer (0.354 g, 0.8 mmol). Reaction proceeds with evolution of N2 gas. Reaction mixture was stirred at 25° C. for 0.5 h. Completion of reaction was confirmed by TLC and reaction mixture was poured into water (100 mL). Organic layer was separated; aqueous layer was again extracted with of DCM (250 mL). Combined organic layer was washed with water (100 mL) and then with aqueous saturated sodium bicarbonate (300 mL) followed by brine (75 mL). Organic layer was dried over anhydrous sodium sulfate, sodium sulfate was filtered and washed with DCM (100 mL) and solvent was evaporated under reduced pressure using rotavapour to get required crude product. The crude product was purified by column chromatography using silica gel 100-200 mesh, mobile phase hexanes to 35% ethyl acetate in hexanes. Removal of solvent from appropriate fractions under reduced pressure in rotavapour gave pure product.

Workup

  1. customReaction
  2. customReaction mixture
  3. customCompletion of reaction
  4. customwas confirmed by TLC and reaction mixture
  5. customOrganic layer was separated
  6. extractionaqueous layer was again extracted with of DCM (250 mL)
  7. washCombined organic layer was washed with water (100 mL)
  8. dry with materialOrganic layer was dried over anhydrous sodium sulfate, sodium sulfate
  9. filtrationwas filtered
  10. washwashed with DCM (100 mL) and solvent
  11. customwas evaporated under reduced pressure
  12. customto get required crude product
  13. customThe crude product was purified by column chromatography
  14. customRemoval of solvent from appropriate fractions under reduced pressure in rotavapour
  15. customgave pure product

Sources & evidence

ORD record
ord-09cabbaf10274530884bb3c09d2552ba
Source dataset
uspto-grants-2016_05
Patent number
US09340506B2

Reaction notes

Loading…