Hydrochloric Acid → HCID 67176661, compound

HRID 2355262Notes

Reaction equation

HRID 2355262 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][Si](C(C)(C)C)(C)C)=[CH:4][C:3]=1[O:16][Si](C(C)(C)C)(C)C.C([Li])(C)(C)C.CCCCC.[CH:34]1([CH2:37][C:38](N(OC)C)=[O:39])[CH2:36][CH2:35]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.Cl>C(OCC)C.O>[CH:34]1([CH2:37][C:38]([C:2]2[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=2[OH:16])=[O:39])[CH2:36][CH2:35]1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 8003PentaneHCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 224737662-cyclopropyl-N-methoxy-N-methylacetamideHCID 60205807HCID 60205807, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 67176661HCID 67176661, compoundYield 94.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Procedure

Stir 1-bromo-2,4-bis-(tert-butyl-dimethyl-silanyloxy)-benzene (100 g, 240 mmol) in diethyl ether (1 L, anhydrous) at −60° C. and treat with 1.7M tert-butyllithium in pentane (290 mL, 493 mmol) via addition funnel over a 10 minute period. Stir for 15 min, then treat with 2-cyclopropyl-N-methoxy-N-methyl-acetamide (34 g, 237 mmol) in a minimum amount of ethyl ether. Remove cold bath, stir for 1 hr, treat with 1N aqueous hydrochloric acid (100 mL), and stir for an additional hour. Separate the layers and wash the organic layer with 1N aqueous hydrochloric acid (100 mL), brine, dry with magnesium sulfate, filter, and evaporate. Dissolve the residue in tetrahydrofuran (1 L), treat with 1N tetrabutylammonium fluoride solution in tetrahydrofuran (500 mL, 500 mmol), and stir for 3 hrs. Pour mixture into 1 L of water containing 120 mL of 5N hydrochloric acid, separate layers, and extract water layer twice with ethyl acetate. Wash organic layers with brine, dry with magnesium sulfate, filter, and evaporate. Chromatograph residue on silica gel (Biotage® Radial Compression fitted with a 75-L column) eluting with 25% ethyl acetate in hexanes to isolate the title compound (43 g, 94% yield). 1H NMR (CDCl3) δ 12.83 (s, 1H), 7.60 (d, J=8.0 Hz, 1H), 6.39 (m, 2H), 5.98 (s, 1H), 2.80 (d, J=4.0 Hz, 2H), 1.13 (m, 1H), 0.60 (m, 2H), 0.22 (m, 2H).

Workup

  1. customRemove cold bath
  2. stirringstir for 1 hr
  3. additiontreat with 1N aqueous hydrochloric acid (100 mL)
  4. stirringstir for an additional hour
  5. customSeparate the layers
  6. washwash the organic layer with 1N aqueous hydrochloric acid (100 mL), brine
  7. dry with materialdry with magnesium sulfate
  8. filtrationfilter
  9. customevaporate
  10. dissolutionDissolve the residue in tetrahydrofuran (1 L)
  11. stirringstir for 3 hrs
  12. customseparate layers
  13. extractionextract water layer twice with ethyl acetate
  14. dry with materialWash organic layers with brine, dry with magnesium sulfate
  15. filtrationfilter
  16. customevaporate
  17. customChromatograph residue on silica gel (Biotage® Radial Compression fitted with a 75-L column)
  18. washeluting with 25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f72bba7bb1a943a4a508e8630cc3a861
Source dataset
uspto-grants-2010_07
Patent number
US07754742B2

Reaction notes

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