Triethylamine → Methanesulfonic acid 2-(1-benzyl-1H-indazol-6-yl)-2-methanesulfonyloxy-ethyl ester

HRID 1410340Notes

Reaction equation

HRID 1410340 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH:17]([OH:20])[CH2:18][OH:19])[CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C(Cl)Cl>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH:17]([O:20][S:29]([CH3:28])(=[O:31])=[O:30])[CH2:18][O:19][S:29]([CH3:28])(=[O:31])=[O:30])[CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 674495831-(1-Benzyl-1H-indazol-6-yl)-ethane-1,2-diol

Product 1

HCID 76800943Methanesulfonic acid 2-(1-benzyl-1H-indazol-6-yl)-2-methanesulfonyloxy-ethyl esterYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(1-Benzyl-1H-indazol-6-yl)-ethane-1,2-diol (0.27 g, 1.0 mmol) and Et3N (0.35 mL, 2.5 mmol) in dry CH2Cl2 (5 mL) was cooled in an ice bath before dropwise addition of MsCl (0.155 mL, 2.0 mmol) over 5 min. The resulting mixture was left to stir for 2 h, warming slowly to RT. After dilution with further CH2Cl2, the solution was washed quickly with 1.0 M aq. HCl (20 mL), sat. aq. NaHCO3 (40 mL) and brine (20 mL), dried over Na2SO4, filtered and concentrated at 25° C. to afford the crude product. The crude product was part-purified by rapid column chromatography on silica using 1:1 Et2O/CH2Cl2 as eluent, again concentrating at 25° C., giving the title compound (0.30 g, 71%) as an off-white, gummy foam. 1H NMR: (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.81 (d, J=8.3 Hz, 1H), 7.42 (s, 1H), 7.34-7.23 (m, 3H), 7.17 (dd, J=18.1, 7.6 Hz, 3H), 5.89 (dd, J=8.5, 3.2 Hz, 1H), 5.66 (d, J=15.8 Hz, 1H), 5.60 (d, J=15.8 Hz, 1H), 4.52 (dd, J=11.8, 8.6 Hz, 1H), 4.40 (dd, J=11.8, 3.2 Hz, 1H), 3.04 (s, 3H), 2.75 (s, 3H). MS (ES+): 425 ([M+H]+), calcd for [C18H20N2O6S2+H]+ 425.1.

Workup

  1. waitThe resulting mixture was left
  2. washAfter dilution with further CH2Cl2, the solution was washed quickly with 1.0 M aq. HCl (20 mL), sat. aq. NaHCO3 (40 mL) and brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated at 25° C.
  6. customto afford the crude product
  7. customThe crude product was part-purified by rapid column chromatography on silica using 1:1 Et2O/CH2Cl2 as eluent
  8. concentrationagain concentrating at 25° C.

Sources & evidence

ORD record
ord-4d7252ea4c434fc895bfd52eff932d17
Source dataset
uspto-grants-2014_12
Patent number
US08921545B2

Reaction notes

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