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

HRID 1751836Notes

Reaction equation

HRID 1751836 reaction equation
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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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 0118.5, 73.4, 67.6, 66.6, 40.9, 32.0, 28.1, 23.9.19H25ClN2O3: 365.162647, found 365.1624.

Workup

  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

Sources & evidence

ORD record
ord-f73870ca57d447be96f39cf4df52ae3f
Source dataset
uspto-grants-2015_10
Patent number
US09161997B2

Reaction notes

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