Dimethyl Sulfoxide → HCID 57911419, compound

HRID 1099160Notes

Reaction equation

HRID 1099160 reaction equation
CS(C)=O.[N:5]1[CH:10]=[CH:9][CH:8]=[C:7]2[CH2:11][CH:12]([OH:16])[CH2:13][CH2:14][CH2:15][C:6]=12.CCN(CC)CC.O>C(Cl)Cl>[N:5]1[CH:10]=[CH:9][CH:8]=[C:7]2[CH2:11][C:12](=[O:16])[CH2:13][CH2:14][CH2:15][C:6]=12

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 962WaterHCID 8471TriethylamineHCID 57911446HCID 57911446, compound

Product 1

HCID 57911419HCID 57911419, compoundYield 86.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In an oven-dried 500 mL round-bottomed flask was OXALYL CHLORIDE (3.42 mL, 39.1 mmol) in CH2Cl2 (100 mL) to give a colorless solution at −55° C. under nitrogen. DMSO (5.54 mL, 78 mmol) was added dropwise over 10 min. After the solution was stirred for an additional 30 min, 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-6-ol (5.79 g, 35.5 mmol) (azeotroped with dry benzene) dissolved in 20 ml CH2Cl2 (plus 20 ml rinse) was added via canuula over 5 min. The reaction mixture was stirred at −50-−55° C. for an additional 40 min (the solution became milky). Et3N (24.74 mL, 178 mmol) was added via syringe at −50° C. and the reaction mixture was stirred for 30 min (Gel like and difficult to stir. Needs occasional shaking at ambient temperature). 100 ml water was added, and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2×100 ml). The combined organic layers were dried with Na2SO4, and concentrated to a tan oil with some solids. Purification by FCC up to 10% MeOH/CH2Cl2 afforded the desired product as an orange oil (4.947 g, 86% for 4 steps). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.28-8.38 (m, 1H) 7.37 (d, J=7.63 Hz, 1H) 7.00-7.13 (m, 1H) 3.65 (s, 2H) 3.10-3.18 (m, 2H) 2.50-2.60 (m, 2H) 2.01 (dd, J=6.71, 4.88 Hz, 2H); 13C NMR (126 MHz, CHLOROFORM-d) δ ppm 207.23 (s, 1C) 160.24 (s, 1C) 147.98 (s, 1C) 137.20 (s, 1C) 128.85 (s, 1C) 122.25 (s, 1C) 48.89 (s, 1C) 43.96 (s, 1C) 36.15 (s, 1C) 24.70 (s, 1C).

Workup

  1. wash(plus 20 ml rinse)
  2. additionwas added via canuula over 5 min
  3. stirringThe reaction mixture was stirred at −50-−55° C. for an additional 40 min (the solution
  4. stirringthe reaction mixture was stirred for 30 min
  5. stirring(Gel like and difficult to stir. Needs occasional shaking at ambient temperature)
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with CH2Cl2 (2×100 ml)
  8. dry with materialThe combined organic layers were dried with Na2SO4
  9. concentrationconcentrated to a tan oil with some solids
  10. customPurification by FCC up to 10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-d0c6641d30b74130adcb1445af5750f6
Source dataset
uspto-grants-2012_03
Patent number
US08143403B2

Reaction notes

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