Potassium Phosphate, Tribasic → Methyl 2-{[(3-methylisoxazol-5-yl)methyl]amino}-benzoate

HRID 16769

반응식

HRID 16769 반응식
[CH3:1][C:2]1[CH:6]=[C:5]([CH2:7][NH2:8])[O:4][N:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.I[C:47]1[CH:56]=[CH:55][CH:54]=[CH:53][C:48]=1[C:49]([O:51][CH3:52])=[O:50]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:1][C:2]1[CH:6]=[C:5]([CH2:7][NH:8][C:47]2[CH:56]=[CH:55][CH:54]=[CH:53][C:48]=2[C:49]([O:51][CH3:52])=[O:50])[O:4][N:3]=1

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 69132Benzoic acid, 2-iodo-, methyl esterHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 16481072(3-Methylisoxazol-5-yl)methanamine

생성물 1

HCID 57440405Methyl 2-{[(3-methylisoxazol-5-yl)methyl]amino}-benzoate수율 45.6%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

1-(3-Methylisoxazol-5-yl)methanamine (155 mg, 1.37 mmol, 1.2 eq), potassium phosphate (341 mg, 1.60 mmol, 1.4 eq), S-Phos (95 mg, 0.230 mmol, 0.2 eq) and Pd2dba3 (13 mg, 0.06 mmol, 0.05 eq) were stirred in toluene (5 ml) under nitrogen. Methyl 2-iodobenzoate (300 mg, 1.14 mmol, 1 eq) was added and the mixture was stirred at room temperature for 3 days, then at 90° C. for 6 h. The reaction mixture was allowed to cool, poured into water (100 ml) and extracted with ethyl acetate (3×60 ml). The combined extracts were washed with brine, dried over MgSO4, filtered and evaporated. The residual gummy oil was triturated with ether resulting in precipitation of a small amount of a yellow solid which was filtered off. The filtrate was evaporated and triturated again with methanol and a second precipitate was removed by filtration. The filtrate was evaporated, then purified by silica column chromatography, eluting with DCM. The product fractions were evaporated to afford methyl 2-{[(3-methylisoxazol-5-yl)methyl]amino}-benzoate as a yellow oily gum (128 mg, 45% yield); 1H NMR (399.902 MHz, CDCl3) δ 2.25 (s, 3H), 3.88 (s, 3H), 4.53 (d, 2H), 5.99 (s, 1H), 6.62-6.70 (m, 2H), 7.32-7.38 (m, 1H), 7.92-7.96 (m, 1H), 8.19 (t, 1H). MS: m/z 247 (MH+)

후처리

  1. waitat 90° C. for 6 h
  2. temperatureto cool
  3. extractionextracted with ethyl acetate (3×60 ml)
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residual gummy oil was triturated with ether resulting in precipitation of a small amount of a yellow solid which
  9. filtrationwas filtered off
  10. customThe filtrate was evaporated
  11. customtriturated again with methanol
  12. customa second precipitate was removed by filtration
  13. customThe filtrate was evaporated
  14. custompurified by silica column chromatography
  15. washeluting with DCM
  16. customThe product fractions were evaporated

출처 및 근거

ORD 기록
ord-2140c456723b4dd89e67c4192e737bb4
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07737149B2

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