Water → 3-Benzamido-3-(4-chlorophenyl)cyclobutanecarboxylic acid

HRID 1778590Notes

Reaction equation

HRID 1778590 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2(O)[CH2:11][CH:10]([C:12]([OH:14])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.[C:16](#[N:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.O.[O-:25]S(C(F)(F)F)(=O)=O.[Bi+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>C(OCC)C.CCCCCCC>[C:16]([NH:23][C:8]1([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH2:11][CH:10]([C:12]([OH:14])=[O:13])[CH2:9]1)(=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7505BenzonitrileHCID 9917655Bi(OTf)3HCID 755396183-(4-Chlorophenyl)-3-hydroxycyclobutane-1-carboxylic acid

Product 1

HCID 895142713-Benzamido-3-(4-chlorophenyl)cyclobutanecarboxylic acidYield 143%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8900HeptaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-(4-chlorophenyl)-3-hydroxycyclobutanecarboxylic acid (4 g, 0.0176 mol) and benzonitrile (8.66 mL, 0.0847 mol) in water (4.4 mL, 0.245 mol) was treated with bismuth triflate (2.32 g, 0.0035 mol) and heated to 100° C. for 16 h. After cooling to 0° C., the reaction was quenched with 1 M HCl to pH˜, dichloromethane was added, the solution was stirred vigorously and the phases were separated. The product was leached from organic layer with 1 M NaOH. This aqueous solution was acidified with to pH-3 with 6 M HCl and extracted two times with diethyl ether. The combined organic layers were dried over MgSO4, filtered and concentrated to give a light brown residue. This crude product was dissolved in diethyl ether, and diluted with n-heptane to precipitate the product. It was filtrated, washed with n-heptane and dried at 45° C. to give the product as a white crystalline solid (1.65 g, 29%). 1H NMR (DMSO-d6, 600 MHz) δ 12.25 (bs, 1H), 9.16 (s, 1H), 7.82 (d, J=7.2 Hz, 2H), 7.50-7.53 (m, 3H), 7.43-7.45 (m, 2H), 7.38 (d, J=8.7 Hz, 2H), 2.94-3.00 (m, 1H), 2.72-2.78 (m, 4H). ESI MS found for C18H16ClNO3 m/z [352.3/354, 3 (M+Na+), 330.4/332.4 (M+1), 328.2/330.2 (M−1)].

Workup

  1. temperatureAfter cooling to 0° C.
  2. customthe reaction was quenched with 1 M HCl
  3. additiondichloromethane was added
  4. customthe phases were separated
  5. extractionextracted two times with diethyl ether
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a light brown residue
  10. customto precipitate the product
  11. filtrationIt was filtrated
  12. washwashed with n-heptane
  13. customdried at 45° C.

Sources & evidence

ORD record
ord-9c1f4eab30a746ba93eb073829edd506
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

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