Dimethyl Sulfoxide → HCID 67438705, compound

HRID 1879370Notes

Reaction equation

HRID 1879370 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH:11]([Si:14]([CH:31]([CH3:33])[CH3:32])([CH:28]([CH3:30])[CH3:29])[O:15][C@@H:16]1[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[CH2:20][C@@H:19]([OH:27])[CH2:18][CH2:17]1)([CH3:13])[CH3:12].C(N(CC)CC)C>C(Cl)Cl.C(OCC)(=O)C.O>[CH:31]([Si:14]([CH:11]([CH3:13])[CH3:12])([CH:28]([CH3:30])[CH3:29])[O:15][C@@H:16]1[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[CH2:20][C:19](=[O:27])[CH2:18][CH2:17]1)([CH3:33])[CH3:32]

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 67115935HCID 67115935, compound

Product 1

HCID 67438705HCID 67438705, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

In an oven-dried 250 mL round-bottom flask was dissolved oxalyl chloride (9.54 mL, 19.08 mmol) in methylene chloride (40 mL) to give a colorless solution at −55° C. under nitrogen. DMSO (2.71 mL, 38.2 mmol) was added dropwise slowly over 2 min. After the solution was stirred for an additional 30 min, (6S,9S)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-6-ol (2.91 g, 8.67 mmol) (crude, azeotroped with dry benzene) dissolved in 8 mL methylene chloride (plus 8 mL rinse) was added via cannula over 5 min. The reaction mixture was stirred at −50 to −55° C. for an additional 40 min. Triethylamine (6.04 mL, 43.4 mmol) was added via syringe at −50° C. and the reaction mixture was gradually warmed up to −20° C. for 30 min. TLC showed complete conversion. Water and ethyl acetate were added, and the layers were separated. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried with sodium sulfate, and concentrated to give a tan oil. Purification by FCC up to 50% ethyl acetate/hexane afforded the desired product as a light yellow oil (2.08 g, 72%). MS(ESI)[M+H+]=334.35; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.39 (d, J=5.04 Hz, 1H) 7.49 (d, J=7.55 Hz, 1H) 7.19 (dd, J=7.55, 4.78 Hz, 1H) 5.26 (dd, J=4.78, 2.27 Hz, 1H) 4.69 (d, J=14.35 Hz, 1H) 3.29 (d, J=14.35 Hz, 1H) 3.02 (ddd, J=12.15, 9.00, 6.04 Hz, 1H) 2.45-2.59 (m, 1H) 2.31-2.45 (m, 1H) 2.06-2.25 (m, J=8.53, 8.53, 5.98, 2.39 Hz, 1H) 1.06-1.19 (m, 3H) 1.01 (d, J=7.30 Hz, 9H) 0.89-0.97 (m, 9H).

Workup

  1. customto give a colorless solution at −55° C. under nitrogen
  2. wash(plus 8 mL rinse)
  3. additionwas added via cannula over 5 min
  4. stirringThe reaction mixture was stirred at −50 to −55° C. for an additional 40 min
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. dry with materialThe combined organic layers were dried with sodium sulfate
  8. concentrationconcentrated
  9. customto give a tan oil
  10. customPurification by FCC up to 50% ethyl acetate/hexane

Sources & evidence

ORD record
ord-f40cb238eeb249ab9a81d93f1b147c8f
Source dataset
uspto-grants-2012_11
Patent number
US08314117B2

Reaction notes

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