Pyridine → Tert-butyl 6-methyl-1,2,3-oxathiazinane-3-carboxylate 2-oxide

HRID 1521706Notes

Reaction equation

HRID 1521706 reaction equation
[S:1](Cl)(Cl)=[O:2].[OH:5][CH:6]([CH3:17])[CH2:7][CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13].N1C=CC=CC=1.C(OCC)(=O)C>C(#N)C.CN(C1C=CN=CC=1)C>[CH3:17][CH:6]1[O:5][S:1](=[O:2])[N:9]([C:10]([O:11][C:12]([CH3:13])([CH3:15])[CH3:14])=[O:16])[CH2:8][CH2:7]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 8857Ethyl AcetateHCID 24386Thionyl ChlorideHCID 22499834tert-butyl N-(3-hydroxybutyl)carbamate

Product 1

HCID 67235111Tert-butyl 6-methyl-1,2,3-oxathiazinane-3-carboxylate 2-oxideYield 96%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent2×

Procedure

A stirred solution of thionyl chloride (2.0 mL, 27.9 mmol) in acetonitrile (15 mL) is cooled down to −45° C. and a solution of tert-butyl (3-hydroxybutyl)carbamate (2.1 g, 11.2 mmol) in acetonitrile (20 mL) is added by syringe over about 10 min, keeping the internal temperature below −40° C. Then DMAP (136 mg, 1.1 mmol) is added followed by the dropwise addition of pyridine (4.5 mL, 55.8 mmol) by syringe, keeping the temperature below −40° C. The addition takes 1.5 h. Ethyl acetate (50 mL) is added to the suspension. The mixture is filtered at −35° C. to remove the solid and the solid is washed with EtOAc before it is discarded. Then the filtrates are combined, and sat. Na2HPO4 solution (20 mL) is added. Again the mixture is stirred vigorously for 30 min. Then the organic layer is separated, washed with 1M NaHSO4 to remove residual pyridine, dried (MgSO4) and concentrated to afford the title compound as an oil (2.52 g, 96%) which is used in the next step without purification.

Workup

  1. customthe internal temperature below −40° C
  2. customthe temperature below −40° C
  3. additionThe addition
  4. filtrationThe mixture is filtered at −35° C.
  5. customto remove the solid
  6. washthe solid is washed with EtOAc before it
  7. additionsat. Na2HPO4 solution (20 mL) is added
  8. customThen the organic layer is separated
  9. washwashed with 1M NaHSO4
  10. customto remove residual pyridine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-405bb1891043487daeb91171a6205512
Source dataset
uspto-grants-2015_07
Patent number
US09073926B2

Reaction notes

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