Chloromethyl Methyl Ether → 2-(Methoxymethyl)-7-methyl-2H-indazole-5-carbaldehyde

HRID 2099789노트

반응식

HRID 2099789 반응식
[CH3:1][C:2]1[CH:3]=[C:4]([CH:11]=[O:12])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.CN(C1CCCCC1)C1CCCCC1.[CH3:27][O:28][CH2:29]Cl>O1CCCC1.C(OCC)(=O)C>[CH3:27][O:28][CH2:29][N:8]1[CH:7]=[C:6]2[C:10]([C:2]([CH3:1])=[CH:3][C:4]([CH:11]=[O:12])=[CH:5]2)=[N:9]1

참가 물질

6

반응물 3

HCID 7864Chloromethyl Methyl EtherHCID 24210N-Methyl dicyclohexylamineHCID 184521067-Methyl-1H-indazole-5-carbaldehyde

생성물 1

HCID 577946242-(Methoxymethyl)-7-methyl-2H-indazole-5-carbaldehyde수율 58%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 7-methylindazole-5-carboxaldehyde (8.80 g, 54.9 mmol) and N-methyl-dicyclohexylamine (23.6 mL, 110 mmol) in tetrahydrofuran (200 mL) at 0° C. was added chloromethyl methyl ether (7.50 mL, 1.8 equiv). The reaction was allowed to gradually warm to room temperature overnight. The reaction was concentrated, dissolved in diethyl ether, washed with water, then 1 M hydrochloric acid, then water, then brine, dried over magnesium sulfate, and concentrated to give an oil. The oil was dissolved in ethyl acetate and treated with hexanes until lasting turbidity. The suspension was heated until a clear solution was obtained and the flask placed in the freezer. The resulting crystalline solid was crushed with a spatula to break it up, reheated to dissolve some of the solids, and placed in the freezer. The solids were filtered, washed with very cold ether (−78° C.), and air-dried to give 5.43 g. The mother liquor was concentrated, redissolved in ca. 20 mL ether, cooled to −78° C., and treated with a seed crystal of the product. After 1 h, the resulting solids were filtered, washed with cold ether (−78° C.), and air-dried to give an additional 1.05 g (total yield=58%). 1H-NMR (CDCl3, 500 MHz) δ 2.66 (s, 3H), 3.44 (s, 3H), 5.73 (s, 2H), 7.59 (s, 1H), 8.09 (s, 1H), 8.32 (s, 1H), 9.97 (s, 1H). Mass spec.: 205.19 (MH)+.

후처리

  1. concentrationThe reaction was concentrated
  2. dissolutiondissolved in diethyl ether
  3. washwashed with water
  4. dry with material1 M hydrochloric acid, then water, then brine, dried over magnesium sulfate
  5. concentrationconcentrated
  6. customto give an oil
  7. temperatureThe suspension was heated until a clear solution
  8. customwas obtained
  9. customThe resulting crystalline solid was crushed with a spatula
  10. dissolutionto dissolve some of the solids
  11. filtrationThe solids were filtered
  12. washwashed with very cold ether (−78° C.)
  13. customair-dried
  14. customto give 5.43 g
  15. concentrationThe mother liquor was concentrated
  16. dissolutionredissolved in ca. 20 mL ether
  17. temperaturecooled to −78° C.
  18. additiontreated with a seed crystal of the product
  19. filtrationthe resulting solids were filtered
  20. washwashed with cold ether (−78° C.)
  21. customair-dried
  22. customto give an additional 1.05 g (total yield=58%)

출처 및 근거

ORD 기록
ord-9860cc0366d041e383eacd93bd69199a
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07569578B2

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