Methanol → HCID 67468989, compound

HRID 540360Notes

Reaction equation

HRID 540360 reaction equation
C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[Cl:12][C:13]1[CH:27]=[CH:26][C:16]([C:17]([NH:19][CH:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[O:18])=[C:15]([CH2:28][CH2:29]O)[CH:14]=1.C(N(CC)CC)C.CO>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:12][C:13]1[CH:14]=[C:15]2[C:16](=[CH:26][CH:27]=1)[C:17](=[O:18])[N:19]([CH:20]1[CH2:21][CH2:22][O:23][CH2:24][CH2:25]1)[CH2:29][CH2:28]2

Participants

7

Reactant 4

HCID 887MethanolHCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 674660274-Chloro-2-(2-hydroxy-ethyl)-N-(tetrahydro-pyran-4-yl)-benzamide

Product 1

HCID 67468989HCID 67468989, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A round bottomed flask was charged with p-toluenesulfonyl chloride (1.85 g, 9.7 mmol, 2.2 equiv.) and 40 mL of DCM. The solution was cooled to an ice-water bath and evacuated and purged with nitrogen. To this solution was added a solution of 4-chloro-2-(2-hydroxy-ethyl)-N-(tetrahydro-pyran-4-yl)-benzamide (1.25 g, 4.4 mmol, 1 equiv.) in 40 mL of DCM, followed by triethylamine (1.5 ml, 11 mmol, 2.5 equiv.) and a few crystals of DMAP. The solution was stirred under nitrogen overnight from 0° C. to rt. TLC (5% MeOH in DCM for SM) showed the reaction was almost complete. LC/MS: 266 at 2.050 min; SM of 284 at 2.35 min. The reaction was quenched by addition of 1.6 g of polymer-supported ethyleneamine and stirred for 30 min. The reaction solution was filtered through a Celite pad, rinsed with DCM and concentrated to dryness. The residue was re-dissolved in 30 mL of DCM, washed with 10 mL of NaHCO3 aq. The aqueous layer was extracted with DCM (3×5 mL). The combined organic solutions were washed with brine (5 mL), dried (K2CO3), filtered and concentrated. The crude product was purified on a 50-g silica gel column, eluted with 2.5% 7N NH3 of MeOH in DCM to get 110 mg (10% yield) of the title compound as a light yellow solid.

Workup

  1. temperatureThe solution was cooled to an ice-water bath
  2. customevacuated
  3. custompurged with nitrogen
  4. waitLC/MS: 266 at 2.050 min
  5. customThe reaction was quenched by addition of 1.6 g of polymer-supported ethyleneamine
  6. stirringstirred for 30 min
  7. filtrationThe reaction solution was filtered through a Celite pad
  8. washrinsed with DCM
  9. concentrationconcentrated to dryness
  10. dissolutionThe residue was re-dissolved in 30 mL of DCM
  11. washwashed with 10 mL of NaHCO3 aq. The aqueous layer
  12. extractionwas extracted with DCM (3×5 mL)
  13. washThe combined organic solutions were washed with brine (5 mL)
  14. dry with materialdried (K2CO3)
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe crude product was purified on a 50-g silica gel column
  18. washeluted with 2.5% 7N NH3 of MeOH in DCM

Sources & evidence

ORD record
ord-18fab9fcdf68408b9a864263c128f999
Source dataset
uspto-grants-2014_10
Patent number
US08871788B2

Reaction notes

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