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

HRID 1520855Notes

Reaction equation

HRID 1520855 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-f96124c60dd44ea5a25d903a629241f5
Source dataset
uspto-grants-2015_07
Patent number
US09073871B2

Reaction notes

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