Dimethyl Sulfoxide → HCID 121362282, compound

HRID 874756Notes

Reaction equation

HRID 874756 reaction equation
CS(C)=O.C(=O)=O.CC(C)=O.C(Cl)(=O)C(Cl)=O.[C:18]([O:22][C:23](=[O:40])[NH:24][C@H:25]1[CH2:30][CH:29]([OH:31])[CH2:28][S:27][C@@H:26]1[C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[F:39])([CH3:21])([CH3:20])[CH3:19].C(N(CC)CC)C>C(Cl)Cl>[C:18]([O:22][C:23](=[O:40])[NH:24][C@H:25]1[CH2:30][C:29](=[O:31])[CH2:28][S:27][C@@H:26]1[C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[F:39])([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 18522661Acetone cardiceHCID 121362278HCID 121362278, compound

Product 1

HCID 121362282HCID 121362282, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

DMSO (503 μL, 7.09 mmol) was added to a dry ice/acetone cooled solution of oxalyl chloride (253 μL, 2.84 mmol) in methylene chloride (5.0 mL). After 2 min, a solution of tert-butyl[(2R,3S)-2-(2,5-difluorophenyl)-5-hydroxytetrahydro-2H-thiopyran-3-yl]carbamate (490 mg, 1.42 mmol) in methylene chloride (5.0 mL) was added and the mixture was stirred for 30 min. Triethylamine (1.98 mL, 14.2 mmol) was added and the solution was stirred for 10 min and then removed from the dry ice/acetone bath and warmed to room temperature. Methylene chloride (50 mL) and water (30 mL) were added and the organic phase was dried with sodium sulfate, filtered and evaporated to an oil. The residue was placed onto preparative tlc plates, developed with 1:2 EtOAc/hexanes and eluted with EtOAc to give the title compound as a solid. The mixture was resolved by preparative HPLC Chiralpak AD chromatography eluting with 25% IPA/heptane to give the first eluting isomer, namely, tert-butyl[(2S,3R)-2-(2,5-difluorophenyl)-5-oxotetrahydro-2H-thiopyran-3-yl]carbamate and the second eluting title compound isomer, namely, tert-butyl[(2R,3S)-2-(2,5-difluorophenyl)-5-oxotetrahydro-2H-thiopyran-3-yl]carbamate.

Workup

  1. stirringthe solution was stirred for 10 min
  2. customremoved from the dry ice/acetone bath
  3. additionMethylene chloride (50 mL) and water (30 mL) were added
  4. dry with materialthe organic phase was dried with sodium sulfate
  5. filtrationfiltered
  6. customevaporated to an oil
  7. washeluted with EtOAc

Sources & evidence

ORD record
ord-ff3c61e736dd43e786659482d5396408
Source dataset
uspto-grants-2015_03
Patent number
US08980929B2

Reaction notes

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