Tavaborole → Methanesulfonic acid 6-(4-fluoro-2-hydroxymethyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester

HRID 916873Notes

Reaction equation

HRID 916873 reaction equation
[CH3:1][S:2]([O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12]([C:16](=[O:32])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:19][CH:18]=1)=[C:11](OS(C(F)(F)F)(=O)=O)[CH:10]=[CH:9]2)(=[O:4])=[O:3].[F:41][C:42]1[CH:51]=[CH:50][C:45]2B(O)[O:47][CH2:48][C:44]=2[CH:43]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:41][C:42]1[CH:51]=[CH:50][C:45]([C:11]2[C:12]([C:16](=[O:32])[C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][N:26]4[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]4)=[CH:19][CH:18]=3)=[C:13]3[C:8](=[CH:9][CH:10]=2)[CH:7]=[C:6]([O:5][S:2]([CH3:1])(=[O:4])=[O:3])[CH:15]=[CH:14]3)=[C:44]([CH2:48][OH:47])[CH:43]=1

Participants

4

Reactant 2

HCID 11499245TavaboroleHCID 11628623Trifluoromethanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester

Product 1

HCID 58961551Methanesulfonic acid 6-(4-fluoro-2-hydroxymethyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl esterYield 73%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

Charge a 100 mL round bottom flask with trifluoro-methanesulfonic acid 6-methanesulfonyloxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (2.3 g, 3.8 mmol), 5-fluoro-3H-benzo[c][1,2]oxaborol-1-ol (1.16 g, 7.6 mmol) and Pd(PPh3)4 (220 mg, 0.19 mmol) and purge with nitrogen. Add degassed DME (36 mL) and 2M Na2CO3 (4 mL) to the flask and plunge into a 75° C. oil bath and stir overnight. Pour the reaction into saturated aqueous sodium bicarbonate and extract with methylene chloride. Wash the organic layer with water and dry with sodium sulfate. Filter and concentrate to an amber foam. Purify the crude material on silica gel (1% to 6% methanol in methylene chloride) to yield 1.6 g (73%) of the title compound as a tan foam. 1H NMR (CDCl3) δ7.98 (d, J=8.4 Hz, 1H), 7.90 (d, J=2.5 Hz, 1H), 7.60 (bs, 3H), 7.43 (d, J=8.4 Hz, 1H), 7.35 (d, J=8.6 Hz, 1H), 7.23 (bs, 11), 6.90-6.70 (m, 4H), 4.40-4.25 (m, 2H), 4.12 (m, 2H), 3.23 (s, 3H), 2.76 (t, J=5.4 Hz, 2H), 2.49 (bs, 4H), 1.59 (m, 5H), 1.45 (m, 1H).

Workup

  1. custompurge with nitrogen
  2. additionAdd
  3. customdegassed DME (36 mL) and 2M Na2CO3 (4 mL) to the flask and plunge into a 75° C. oil bath
  4. additionPour
  5. customthe reaction into saturated aqueous sodium bicarbonate
  6. extractionextract with methylene chloride
  7. washWash the organic layer with water
  8. dry with materialdry with sodium sulfate
  9. filtrationFilter
  10. concentrationconcentrate to an amber foam
  11. customPurify the crude material on silica gel (1% to 6% methanol in methylene chloride)

Sources & evidence

ORD record
ord-b3dc8ef1a02c485593322d833569d181
Source dataset
uspto-grants-2007_09
Patent number
US07271264B2

Reaction notes

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