Hydrochloric Acid → Methyl 3-bromo-4-hydroxy-5-(3-morpholino-3-oxopropanoyl)benzoate

HRID 41178노트

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HRID 41178 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([C:14]1[CH:15]=[C:16]([CH:21]=[C:22]([Br:25])[C:23]=1[OH:24])[C:17]([O:19][CH3:20])=[O:18])(=[O:13])[CH3:12].[N:26]1([C:32](Cl)=[O:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.Cl>C1COCC1.O.C(Cl)Cl>[Br:25][C:22]1[CH:21]=[C:16]([CH:15]=[C:14]([C:11](=[O:13])[CH2:12][C:32]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[O:33])[C:23]=1[OH:24])[C:17]([O:19][CH3:20])=[O:18]

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 848104-Morpholinecarbonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 15818980Methyl 3-acetyl-5-bromo-4-hydroxybenzoate

생성물 1

HCID 58235040Methyl 3-bromo-4-hydroxy-5-(3-morpholino-3-oxopropanoyl)benzoate수율 90.2%

시약·촉매·용매 3

HCID 962Water용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a solution of lithium bis(trimethylsilyl)amide (1.41 L, 1406 mmol) at −65° C. under nitrogen was added dropwise methyl 3-acetyl-5-bromo-4-hydroxybenzoate (120 g, 439 mmol) in THF (1.2 L). The solution was allowed to warm to 0° C., and maintained at this temperature for 1 h. The solution was cooled back to −65° C. and morpholine-4-carbonyl chloride (0.055 L, 483 mmol) was added. The mixture was stirred at room temperature for 2 h then cooled to −30° C., DCM (1.5 L) and water (1 L) were added followed by dropwise addition of HCl 6N (500 mL) then HCl 2N (300 mL) until pH 7, the aqueous solution was extracted with DCM (3×). The combined extracts were dried over MgSO4 and evaporated. The crude product was triturated in MTBE to obtain methyl 3-bromo-4-hydroxy-5-(3-morpholino-3-oxopropanoyl)benzoate (153 g, 90%) as a beige solid. Mass Spectrum: m/z [M+H]+=388.

후처리

  1. temperaturemaintained at this temperature for 1 h
  2. temperatureThe solution was cooled back to −65° C.
  3. temperaturethen cooled to −30° C.
  4. extractionHCl 2N (300 mL) until pH 7, the aqueous solution was extracted with DCM (3×)
  5. dry with materialThe combined extracts were dried over MgSO4
  6. customevaporated
  7. customThe crude product was triturated in MTBE

출처 및 근거

ORD 기록
ord-ac98ea7eac74444ebae29bd7fb48f7ea
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530470B2

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