4-(3-Oxobutyl)benzoic acid methyl ester → 4-(4-Hydroxymethylphenyl)butan-2-ol

HRID 1392832노트

반응식

HRID 1392832 반응식
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12](=[O:14])[CH3:13])=[CH:6][CH:5]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[OH:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][CH:12]([OH:14])[CH3:13])=[CH:6][CH:5]=1

참가 물질

4

반응물 2

HCID 109326404-(3-Oxobutyl)benzoic acid methyl esterHCID 21226445Aluminium lithium hydride

생성물 1

HCID 671001364-(4-Hydroxymethylphenyl)butan-2-ol수율 71.2%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of the product of Example 7A (505 mg, 2.447 mmol) in THF (19 mL) at 0° C. was added a 1M solution (in THF) of lithium aluminum hydride (12.2 mL, 12.237 mmol) dropwise. After completion of addition the ice bath was removed and the reaction was stirred at room temperature for 1 hour under nitrogen atmosphere. Then, in succession, was added water (183 μL), 15% NaOH solution (183 μL), and water (548 μL). The reaction stirred for an additional 15 minutes before it was filtered and washed with THF. The filtrate was then concentrated under reduced pressure to obtain 4-(4-hydroxymethyl-phenyl)butan-2-ol as a brown oil (314 mg, 71% yield). Then to a solution of 2-tert-butyl-4-chloro-5-hydroxy-2H-pyridazin-3-one (234 mg, 1.155 mmol) in THF (45 mL) was added 4-(4-hydroxymethylphenyl)butan-2-ol (312 mg, 1.732 mmol), triphenylphosphine (454 mg, 1.732 mmol), and then diisopropyl azodicarboxylate (DIAD, 335 μL, 1.732 mmol). The reaction was stirred at room temperature overnight under nitrogen atmosphere. Thin layer chromatography (100% ethyl acetate) indicated consumption of the pyridazinone starting material and the reaction was concentrated. The crude material was purified by flash column chromatography (4:1 hexane:ethyl acetate to 100% ethyl acetate) to obtain a clear oil (200 mg, 48% yield). 1H NMR (600 MHz, CDCl3): δ 7.73 (s, 1H), 7.32 (d, 2H, J=8.0), 7.24 (d, 2H, J=8.0), 5.30 (s, 1H), 5.27 (s, 2H), 3.83 (m, 1H), 2.80-2.76 (m, 1H), 2.71-2.66 (m, 1H), 1.63 (s, 9H), 1.23 (d, 3H, J=6.2); 13C (CDCl3 159.3, 153.9, 143.2, 132.5, 129.2, 127.6, 125.4, 150 MHz): δ HRMS calcd for C118.5, 73.4, 67.6, 66.6, 40.9, 32.0, 28.1, 23.9.19H25ClN2O3: 365.162647, found 365.1624.

후처리

  1. customwas removed
  2. additionThen, in succession, was added water (183 μL), 15% NaOH solution (183 μL), and water (548 μL)
  3. stirringThe reaction stirred for an additional 15 minutes before it
  4. filtrationwas filtered
  5. washwashed with THF
  6. concentrationThe filtrate was then concentrated under reduced pressure

출처 및 근거

ORD 기록
ord-d4dec54945e04b27bcfe6602bf878a7b
출처 데이터셋
uspto-grants-2008_03
특허 번호
US07344702B2

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