Dimethyl Sulfoxide → Benzyl (4-oxocyclohexyl)carbamate

HRID 545541Notes

Reaction equation

HRID 545541 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([O:18][C:19](=[O:28])[NH:20][C@H:21]1[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23][CH2:22]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>C(Cl)Cl>[CH2:11]([O:18][C:19](=[O:28])[NH:20][CH:21]1[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][CH2:22]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 178523817HCID 178523817, compound

Product 1

HCID 14615292Benzyl (4-oxocyclohexyl)carbamateYield 76.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Dissolve oxalyl chloride (18.4 mL, 211 mmol) in CH2Cl2 (1000 mL), cool below −70° C., and add DMSO (18.0 mL, 253 mmol) via syringe pump over 30 min. Stir for 45 min, and then add portionwise a suspension of trans-(4-hydroxy-cyclohexyl)-carbamic acid benzyl ester (35.00 g, 140 mmol) in CH2Cl2 (1000 mL), while maintaining the temperature below −70° C. Add the suspension by removing a stopper from the reaction flask and quickly pouring in as much of the suspension as possible while keeping the temperature below −70° C., resulting in a slightly turbid solution upon complete addition. Stir the reaction for 90 min, then add triethylamine (97.8 mL, 702 mmol) slowly via syringe. Stir for another hour, and allow the reaction to slowly warm to room temperature overnight. Wash sequentially with water (1500 mL), brine (2×1500 mL), and saturated aqueous NaHCO3 (2×1500 mL). Separate the organic portion and dry (MgSO4), filter, and concentrate under reduced pressure. Triturate the crude residue twice with 4:1 Hexane/EtOAc (500 mL, then 250 mL). (Alternatively, triturate with 15% EtOAc/Hexane. Then only one trituration is required.) Filter and collect the solids and dry at 35° C. in a vacuum oven to obtain 26.44 g of the product. Combine the filtrates of the triturations and concentrate under reduced pressure, followed by trituration of the residue in 9:1 hexane/EtOAc (100 mL) to afford a second crop of 5.70 g, for a combined yield of 32.14 g (93%). ESI MS: m/z 248 [C14H17NO3+H]+; 1H NMR (300 MHz, CDCl3): δ 1.63-1.78 (m, 2H), 2.22-2.27 (m, 2H), 2.32-2.49 (m, 4H), 3.95-4.04 (m, 1H), 4.75 (br s, 1H), 5.11 (s, 2H), 7.29-7.42 (m, 5H)

Workup

  1. temperaturecool below −70° C.
  2. additionadd portionwise
  3. temperaturewhile maintaining the temperature below −70° C
  4. additionAdd the suspension
  5. customby removing a stopper from the reaction flask
  6. additionquickly pouring in as much of the suspension as possible
  7. customthe temperature below −70° C.
  8. customresulting in a slightly turbid solution upon complete addition
  9. stirringStir
  10. customthe reaction for 90 min
  11. stirringStir for another hour
  12. customthe reaction
  13. washWash sequentially with water (1500 mL), brine (2×1500 mL), and saturated aqueous NaHCO3 (2×1500 mL)
  14. customSeparate the organic portion
  15. dry with materialdry (MgSO4)
  16. filtrationfilter
  17. concentrationconcentrate under reduced pressure
  18. customTriturate the crude residue twice with 4:1 Hexane/EtOAc (500 mL
  19. custom(Alternatively, triturate with 15% EtOAc/Hexane
  20. filtration) Filter
  21. customcollect the solids
  22. customdry at 35° C. in a vacuum oven

Sources & evidence

ORD record
ord-e3f2a8e58f384465a750ba33c63bfbd1
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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