3-Phenylpropylamine → 2-methyl-6-{(1R,3S)-3-[2-(3-phenylpropylamino)ethoxy]cyclohexyloxymethyl}benzoic acid

HRID 1353167Notes

Reaction equation

HRID 1353167 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][O:13][C@@H:14]2[CH2:19][CH2:18][CH2:17][C@H:16]([O:20][CH2:21][CH:22]=O)[CH2:15]2)[C:3]=1[C:4]([O:6]C)=[O:5].[C:24]1([CH2:30][CH2:31][CH2:32][NH2:33])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CO>[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][O:13][C@@H:14]2[CH2:19][CH2:18][CH2:17][C@H:16]([O:20][CH2:21][CH2:22][NH:33][CH2:32][CH2:31][CH2:30][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:15]2)[C:3]=1[C:4]([OH:6])=[O:5]

Participants

4

Reactant 2

HCID 162593-PhenylpropylamineHCID 58864603methyl 2-methyl-6-[(1R,3S)-3-(2-oxoethoxy)cyclohexyloxymethyl]benzoate

Product 1

HCID 588645902-methyl-6-{(1R,3S)-3-[2-(3-phenylpropylamino)ethoxy]cyclohexyloxymethyl}benzoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

200 mg of methyl 2-methyl-6-[(1R,3S)-3-(2-oxoethoxy)cyclohexyloxy-methyl]benzoate and 90 μl of 3-phenylpropylamine are dissolved in 5 ml of methanol. 300 mg of 4 Å molecular sieve, which had been dried by heating, are added, and the mixture is stirred at room temperature for two hours. 25 mg of sodium borohydride are then added to the reaction mixture. After 30 minutes, 50 ml of ethyl acetate are added and the molecular sieve is removed from the mixture by filtration through celite. The filtrate is concentrated under reduced pressure, the residue is dissolved in 5 ml of tert-butanol and 0.5 ml of 10 N potassium hydroxide solution are added. The mixture is refluxed for 1 day. After addition of 2 ml of water, the organic phase is removed and the aqueous phase is extracted three times with in each case 20 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate and the solvents are then removed under reduced pressure. This gives 160 mg of 2-methyl-6-{(1R,3S)-3-[2-(3-phenylpropylamino)ethoxy]cyclohexyloxymethyl}benzoic acid as a yellow oil. C26H25NO4 (425.57), MS(ESI): 426 (M+H+).

Workup

  1. custom300 mg of 4 Å molecular sieve, which had been dried
  2. temperatureby heating
  3. additionare added
  4. addition25 mg of sodium borohydride are then added to the reaction mixture
  5. waitAfter 30 minutes
  6. addition50 ml of ethyl acetate are added
  7. customthe molecular sieve is removed from the mixture by filtration through celite
  8. concentrationThe filtrate is concentrated under reduced pressure
  9. dissolutionthe residue is dissolved in 5 ml of tert-butanol
  10. addition0.5 ml of 10 N potassium hydroxide solution are added
  11. temperatureThe mixture is refluxed for 1 day
  12. additionAfter addition of 2 ml of water
  13. customthe organic phase is removed
  14. extractionthe aqueous phase is extracted three times with in each case 20 ml of ethyl acetate
  15. dry with materialThe combined organic phases are dried over magnesium sulfate
  16. customthe solvents are then removed under reduced pressure

Sources & evidence

ORD record
ord-2e0d2a356f774799803d7dc3466c7a83
Source dataset
uspto-grants-2007_05
Patent number
US07220876B2

Reaction notes

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