Thionyl Chloride → HCID 68700682, compound

HRID 1990889Notes

Reaction equation

HRID 1990889 reaction equation
[N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[O:3][C:2]=1S.S(Cl)(Cl)=O.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH2:28])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>CN(C=O)C>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH:28][C:2]2[O:3][C:4]3[C:9]([N:1]=2)=[CH:8][CH:7]=[CH:6][N:5]=3)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 12682914-Amino-1-Boc-piperidineHCID 178527800HCID 178527800, compound

Product 1

HCID 68700682HCID 68700682, compoundYield 19.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To oxazolo[5,4-b]pyridine-2-thiol (1.0 g, 6.57 mmol, 1.0 equiv) was added thionyl chloride (14.1 g, 8.6 mL, 118.3 mmol, 18.0 equiv) and anhydrous DMF (0.56 g, 0.56 mL, 7.23 mmol, 1.1 equiv) and the reaction mixture heated to reflux for 30 min. The solvent was removed under reduced pressure and the crude oil azeotroped twice with xylene to remove excess thionyl chloride. To the crude reaction product was added 4-amino-piperidine-1-carboxylic acid tert-butyl ester (1.97 g, 9.86 mmol, 1.5 equiv) in anhydrous DMF (5 mL) and the solution heated to 60° C. for 18 h. The solution was concentrated by evaporation under reduced pressure and the crude reaction product purified with column chromatography on silica eluting with ethyl acetate/hexane (1:1) to give 0.40 g (19%) of the title compound. 1H NMR (300 MHz, DMSO): δ 1.34 (s, 9H), 1.26-1.40 (m, 2H), 1.84-1.92 (m, 2H), 2.82-2.95 (m, 2H), 3.67-3.76 (m, 1H), 3.82-3.84 (m, 2H), 7.13 (t, J=7.0 Hz, 1H), 7.52 (dd, J=7.0 Hz, J=1.8 Hz, 1H), 7.79 (dd, J=7.0 Hz, J=1.8 Hz, 1H), 8.23 (d, J=7.6 Hz, 1H).

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureto reflux for 30 min
  3. customThe solvent was removed under reduced pressure
  4. customthe crude oil azeotroped twice with xylene
  5. customto remove excess thionyl chloride
  6. customTo the crude reaction product
  7. concentrationThe solution was concentrated by evaporation under reduced pressure
  8. customthe crude reaction product
  9. custompurified with column chromatography on silica eluting with ethyl acetate/hexane (1:1)

Sources & evidence

ORD record
ord-f4c694674f47475eb65c90a5398d45f7
Source dataset
uspto-grants-2010_01
Patent number
US07645753B2

Reaction notes

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