Dibutyltin dichloride → 4-{[6-(2-Morpholin-4-yl-ethoxy)-benzothiazol-2-ylamino]-methyl}-benzoic Acid Methyl Ester

HRID 1174585Notes

Reaction equation

HRID 1174585 reaction equation
[N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:19]=[CH:18][C:13]3[N:14]=[C:15]([NH2:17])[S:16][C:12]=3[CH:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH:20]([C:22]1[CH:31]=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[CH:24][CH:23]=1)=O.C([Sn](Cl)(Cl)CCCC)CCC.C1([SiH3])C=CC=CC=1>C(OCC)(=O)C.C1COCC1>[CH3:29][O:28][C:26](=[O:27])[C:25]1[CH:30]=[CH:31][C:22]([CH2:20][NH:17][C:15]2[S:16][C:12]3[CH:11]=[C:10]([O:9][CH2:8][CH2:7][N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)[CH:19]=[CH:18][C:13]=3[N:14]=2)=[CH:23][CH:24]=1

Participants

7

Reactant 4

HCID 12688Dibutyltin dichlorideHCID 12752PhenylsilaneHCID 15294Methyl 4-FormylbenzoateHCID 224786596-[2-(Morpholin-4-yl)ethoxy]-1,3-benzothiazol-2-amine

Product 1

HCID 207859534-{[6-(2-Morpholin-4-yl-ethoxy)-benzothiazol-2-ylamino]-methyl}-benzoic Acid Methyl EsterYield 42%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a round-bottom flask containing benzothiazole 226 (5.80 g, 20.8 mmol) was added methyl 4-formylbenzoate (5.11 g, 31.1 mmol), followed by THF (8 mL), dibutyltin dichloride (315 mg, 1.04 mmol) and dropwise addition of phenylsilane (3.24 mL, 31.1 mmol). The resulting mixture was stirred overnight at room temperature under nitrogen. The mixture was diluted in ethyl acetate and filtered. The filtrate was partitioned between ethyl acetate and water and the combined organic layers were washed with 1N HCl. The combined acidic layers were neutralized using a saturated aqueous solution of NaHCO3 and the precipitate was extracted with ethyl aceate. The combined organic layers were washed with brine, dried over MgSO4, and concentrated. The resulting crude was purified by flash chromatography using MeOH/CHCl3 (10:90) to afford 227 (3.69 g, 42% yield). 1H NMR: (Acetone-d6) δ (ppm): 8.04 (d, J=8.5 Hz, 2H), 7.65 (d, J=8.8 Hz, 2H), 7.41 (d, J=8.8 Hz, 1H), 7.34 (d, J=2.5 Hz, 1H), 6.94 (dd, J=8.5, 2.7 Hz, 1H), 4.50 (t, J=5.5 Hz, 2H), 3.86 (s, 3H).

Workup

  1. filtrationfiltered
  2. customThe filtrate was partitioned between ethyl acetate and water
  3. washthe combined organic layers were washed with 1N HCl
  4. extractionthe precipitate was extracted with ethyl aceate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe resulting crude was purified by flash chromatography

Sources & evidence

ORD record
ord-a2b0838a83cf4623acf39acaec780550
Source dataset
uspto-grants-2010_11
Patent number
US07838520B2

Reaction notes

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