4-Toluenesulfonyl chloride → 2-[3-Fluoro-6-(methoxy)-1,5-naphthyridin-4-yl]-2-hydroxyethyl 4-methylbenzenesulfonate

HRID 639023Notes

Reaction equation

HRID 639023 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[CH:12]([OH:15])[CH2:13][OH:14])=[N:9][C:8]([O:16][CH3:17])=[CH:7][CH:6]=2.C(N(CC)CC)C.[S:25](Cl)([C:28]1[CH:34]=[CH:33][C:31]([CH3:32])=[CH:30][CH:29]=1)(=[O:27])=[O:26]>ClCCl.O.C(=O)(O)[O-].[Na+].C([Sn](=O)CCCC)CCC>[CH3:32][C:31]1[CH:33]=[CH:34][C:28]([S:25]([O:14][CH2:13][CH:12]([C:11]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([O:16][CH3:17])[N:9]=3)[N:4]=[CH:3][C:2]=2[F:1])[OH:15])(=[O:27])=[O:26])=[CH:29][CH:30]=1

Participants

7

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 671345911-[3-Fluoro-6-(methoxy)-1,5-naphthyridin-4-yl]-1,2-ethanediol

Product 1

HCID 866033622-[3-Fluoro-6-(methoxy)-1,5-naphthyridin-4-yl]-2-hydroxyethyl 4-methylbenzenesulfonateYield 75%

Reagents, catalysts & solvents 3

HCID 61221Dibutyltin oxideCatalystHCID 6344DichloromethaneSolventHCID 86585896Sodium bicarbonate waterSolvent

Procedure

To a solution of 1-[3-fluoro-6-(methoxy)-1,5-naphthyridin-4-yl]-1,2-ethanediol (16.5 g, 71 mmol)) in dichloromethane (200 mL), triethylamine (10 mL) and dibutyltin oxide (350 mg) was added tosyl chloride (13.2 g). After 3 hours, the mixture was diluted with water/sodium bicarbonate and extracted several times with chloroform. The combined organic extracts were dried over magnesium sulfate and evaporated under vacuum. The residue was chromatographed on silica gel eluting with 20-30% ethyl acetate in chloroform to afford the desired product (20.3 g, 75%). MS (+ve ion electrospray) m/z 393 (M+H)+.

Workup

  1. extractionextracted several times with chloroform
  2. dry with materialThe combined organic extracts were dried over magnesium sulfate
  3. customevaporated under vacuum
  4. customThe residue was chromatographed on silica gel eluting with 20-30% ethyl acetate in chloroform

Sources & evidence

ORD record
ord-a24824a6d8f6436ba773bee0138d6b6d
Source dataset
uspto-grants-2010_04
Patent number
US07691850B2

Reaction notes

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