Methanol → 1-(4-Hydroxy-4-methoxychroman-6-yl)cyclopropanecarboxylic acid

HRID 1847364Notes

Reaction equation

HRID 1847364 reaction equation
C[O:2][C:3]([C:5]1([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[O:14][CH2:13][CH2:12][CH2:11]3)[CH2:7][CH2:6]1)=[O:4].O[Li].[OH2:20].[CH3:21][OH:22]>O>[OH:20][C:11]1([O:22][CH3:21])[C:10]2[C:15](=[CH:16][CH:17]=[C:8]([C:5]3([C:3]([OH:2])=[O:4])[CH2:7][CH2:6]3)[CH:9]=2)[O:14][CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 887Methanol2×HCID 168937Lithium hydroxide, monohydrateHCID 59129159methyl 1-(3,4-dihydro-2H-chromen-6-yl)cyclopropane-1-carboxylate

Product 1

HCID 591292881-(4-Hydroxy-4-methoxychroman-6-yl)cyclopropanecarboxylic acidYield 76%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 1-chroman-6-yl-cyclopropanecarboxylic methyl ester (1.4 g, 60 mmol) in MeOH (20 mL) and water (20 mL) was added LiOH.H2O (1.0 g, 240 mmol) in portions at room temperature. The mixture was stirred overnight at room temperature before the MeOH was removed by evaporation under vacuum. Water and Et2O were added and the aqueous layer was separated, acidified with HCl and extracted with EtOAc (50 mL×3). The combined organic extracts dried over anhydrous Na2SO4 and evaporated under vacuum to give 1-(4-Hydroxy-4-methoxychroman-6-yl)cyclopropanecarboxylic acid (1.0 g, 76%). 1H NMR (400 MHz, DMSO) δ 12.10 (br s, 1H), 6.95 (d, J=2.4 Hz, 2H), 6.61-6.59 (m, 1H), 4.09-4.06 (m, 2H), 2.70-2.67 (m, 2H), 1.88-1.86 (m, 2H), 1.37-1.35 (m, 2H), 1.04-1.01 (m, 2H). MS (ESI) m/z (M+H+) 217.4.

Workup

  1. customwas removed by evaporation under vacuum
  2. additionWater and Et2O were added
  3. customthe aqueous layer was separated
  4. extractionextracted with EtOAc (50 mL×3)
  5. dry with materialThe combined organic extracts dried over anhydrous Na2SO4
  6. customevaporated under vacuum

Sources & evidence

ORD record
ord-5f9cbd4fb8f749aba7feba199b112de2
Source dataset
uspto-grants-2015_02
Patent number
US08952050B2

Reaction notes

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