Water → 4-(Cyclobutyl(hydroxy)methyl)benzoic acid

HRID 537481Notes

Reaction equation

HRID 537481 reaction equation
[CH:1]1([CH:5]([OH:17])[C:6]2[CH:16]=[CH:15][C:9]([C:10]([O:12]CC)=[O:11])=[CH:8][CH:7]=2)[CH2:4][CH2:3][CH2:2]1.O1CCCC1.O.O.[OH-].[Li+]>CO>[CH:1]1([CH:5]([OH:17])[C:6]2[CH:16]=[CH:15][C:9]([C:10]([OH:12])=[O:11])=[CH:8][CH:7]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 68157714Ethyl 4-(cyclobutyl(hydroxy)methyl)benzoate

Product 1

HCID 681568354-(Cyclobutyl(hydroxy)methyl)benzoic acidYield 77.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a flask containing ethyl 4-(cyclobutyl(hydroxy)methyl)benzoate (530 mg, 2.26 mmol) was added tetrahydrofuran (5.60 mL), water (5.60 mL), and methanol (5.60 mL). Lithium hydroxide monohydrate (475 mg, 11.3 mmol) was then added. The suspension was stirred at room temperature for 18 hours. The reaction was quenched with 1 N hydrochloric acid to pH 3 and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, and concentrated to give 490 mg of crude material. Purification by silica gel flash chromatography (0-20% ethyl acetate in heptane) afforded 4-(cyclobutyl(hydroxy)methyl)benzoic acid (360 mg, 77%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.07 (d, J=8.2 Hz, 2H), 7.43 (dd, J=8.0, 1.0 Hz, 2H), 4.67 (d, J=7.6 Hz, 1H), 2.62 (d, J=8.0 Hz, 1H), 2.09-1.98 (m, 2H), 1.91-1.80 (m, 4H). MS (M−1): 205.2.

Workup

  1. customThe reaction was quenched with 1 N hydrochloric acid to pH 3
  2. extractionextracted three times with ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give 490 mg of crude material
  7. customPurification by silica gel flash chromatography (0-20% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-73d21a61c75841c38df55931035b4a05
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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