Tetramethyltin → (R,R)-N-[3-(3-fluoro-4-methoxyphenyl)-4-methylisothiazol-5-yl]-2-methylcyclopropanecarboxamide

HRID 2422720Notes

Reaction equation

HRID 2422720 reaction equation
[Sn](C)(C)(C)[CH3:2].Br[C:7]1[C:8]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([F:27])[CH:20]=2)=[N:9][S:10][C:11]=1[NH:12][C:13]([C@@H:15]1[CH2:17][C@H:16]1[CH3:18])=[O:14]>CN(C=O)C.CCOC(C)=O.[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:27][C:21]1[CH:20]=[C:19]([C:8]2[C:7]([CH3:2])=[C:11]([NH:12][C:13]([C@@H:15]3[CH2:17][C@H:16]3[CH3:18])=[O:14])[S:10][N:9]=2)[CH:24]=[CH:23][C:22]=1[O:25][CH3:26]

Participants

7

Reactant 2

HCID 11661TetramethyltinHCID 67180682(R,R)-N-[4-bromo-3-(3-fluoro-4-methoxyphenyl)-isothiazol-5-yl]-2-methylcyclopropanecarboxamide

Product 1

HCID 67182345(R,R)-N-[3-(3-fluoro-4-methoxyphenyl)-4-methylisothiazol-5-yl]-2-methylcyclopropanecarboxamideYield 49.2%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
130 °C

Procedure

Add PdCl2(PPh3)2 (0.15 g, 0.21 mmol) and Sn(CH3)4 (0.79 mL, 1.02 g, 5.71 mmol) to (R,R)—N-[4-bromo-3-(3-fluoro-4-methoxyphenyl)-isothiazol-5-yl]-2-methylcyclopropanecarboxamide (0.55 g, 1.43 mmol) in DMF (3 mL), and stir the reaction mixture at 130° C. in a sealed tube overnight. Dilute with EtOAc (100 mL) and brine (100 mL). Collect the organic phase, dry (K2CO3) and evaporate. Take up the resultant oil in 1:1 MTBE:KF (aqueous, 15%) (50 mL) and stir at reflux for 1 h. Pour the cooled solution over diatomaceous earth and filter with MTBE (100 mL). Collect the organic phase, dry (K2CO3) and evaporate. Chromatography over silica gel, eluting with 10-30% THF in hexane, affords (R,R)—N-[3-(3-fluoro-4-methoxyphenyl)-4-methylisothiazol-5-yl]-2-methylcyclopropanecarboxamide. Yield: 49.2%. ES-MS: m/e 321.0 (m+1).

Workup

  1. customCollect the organic phase
  2. dry with materialdry (K2CO3)
  3. customevaporate
  4. stirringKF (aqueous, 15%) (50 mL) and stir
  5. temperatureat reflux for 1 h
  6. additionPour the cooled solution over diatomaceous earth
  7. filtrationfilter with MTBE (100 mL)
  8. customCollect the organic phase
  9. dry with materialdry (K2CO3)
  10. customevaporate
  11. washChromatography over silica gel, eluting with 10-30% THF in hexane

Sources & evidence

ORD record
ord-6ff032e0b161424e9e3ccdebda2de4b0
Source dataset
uspto-grants-2011_06
Patent number
US07960419B2

Reaction notes

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