Potassium Hydroxide → 1-((4-Methoxy-2,3,5-trimethylphenyl-amino)-methyl)cyclobutane carboxylic acid

HRID 2103064Notes

Reaction equation

HRID 2103064 reaction equation
[CH3:1][O:2][C:3]1[C:8]([CH3:9])=[CH:7][C:6]([NH:10][CH2:11][C:12]2([C:16]([O:18]CC)=[O:17])[CH2:15][CH2:14][CH2:13]2)=[C:5]([CH3:21])[C:4]=1[CH3:22].[OH-].[K+]>C(O)C>[CH3:1][O:2][C:3]1[C:8]([CH3:9])=[CH:7][C:6]([NH:10][CH2:11][C:12]2([C:16]([OH:18])=[O:17])[CH2:13][CH2:14][CH2:15]2)=[C:5]([CH3:21])[C:4]=1[CH3:22]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 86605498Ethyl 1-((4-methoxy-2,3,5-trimethylphenylamino)methyl)-cyclobutanecarboxylate

Product 1

HCID 866054991-((4-Methoxy-2,3,5-trimethylphenyl-amino)-methyl)cyclobutane carboxylic acidYield 96.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of ethyl 1-((4-methoxy-2,3,5-trimethylpheny-lamino)methyl)cyclobutane-carboxylate (500 mg) in ethanol (10 mL), was added a KOH solution (2.5 mL). The mixture was left overnight and the ethanol was evaporated. After addition of water, the mixture was acidified with HCl (3 M) to reach a pH of 1-2. The aqueous phase was extracted with ethylacetate and the organic phase was dried with Na2SO4 and evaporated to give 1-((4-methoxy-2,3,5-trimethylphenyl-amino)-methyl)cyclobutane carboxylic acid (440 mg ) as a foam, which was used for next step. 10 mL of the foam was mixed with toluene (10 mL) and phosphoric acid (1 mL). The mixture was heated up in an oil bath, and after 30 min, the mixture was cooled and quenched with water. Dichloromethane was used to extract the aqueous phase several times. The organic phase was then combined, dried and evaporated to give a solid, which was passed through a column (Hexane: EtOAc; 5:2-5:4) to give 6′-methoxy-5′,7′,8′-trimethyl-1′H-spiro[cyclobutane-1,3′-quinolin]-4′(2′H)-one as a yellow solid. 1H-NMR, (300 MHz, CDCl3) δ=4.18 (s, 1H), 3.6 (s, 3H), 3.53(s, 2H), 2.58(s, 3H), 2.515-2.322 (m, 2H), 2.25 (s, 3H), 2.05 (s, 3H), 2.022-1.769 (m, 4H). ppm. 13C-NMR, (75 MHz, CDCl3) δ=197.89, 147.22, 136.52, 131.29, 118.77, 114.58, 60.48, 50.64, 47.26, 25.89, 14.9, 14.48, 13.78, 12.91 ppm. MS: m/z 260.2 (M+H+)

Workup

  1. customthe ethanol was evaporated
  2. additionAfter addition of water
  3. extractionThe aqueous phase was extracted with ethylacetate
  4. dry with materialthe organic phase was dried with Na2SO4
  5. customevaporated

Sources & evidence

ORD record
ord-860ce50f270647a29339221a479af39c
Source dataset
uspto-grants-2009_08
Patent number
US07576094B2

Reaction notes

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