Potassium Carbonate → HCID 66653710, compound

HRID 2036200Notes

Reaction equation

HRID 2036200 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[OH:28])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O:30][C:31](=[O:45])[C@@H:32](OS(C1C=CC(C)=CC=1)(=O)=O)[CH3:33].C(=O)([O-])[O-].[K+].[K+]>CC#N>[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[O:28][C@@H:32]([C:31]([OH:45])=[O:30])[CH3:33])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12884152Methyl (2S)-2-[(4-methylbenzene-1-sulfonyl)oxy]propanoate2×HCID 66653819HCID 66653819, compound

Product 1

HCID 66653710HCID 66653710, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of (±)-1-(5-chloro-2-hydroxy-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (192 mg, 0.30 mmol, 1.0 eq.) in MeCN (1 mL), (S)-2-(toluene-4-sulfonyloxy)-propionic acid methyl ester (80 mg, 0.30 mmol, 1.0 eq.) and potassium carbonate anhydrous (83 mg, 0.60 mmol, 2.0 eq.) were added and the mixture was heated to 65° C. for 18 hours. (S)-2-(Toluene-4-sulfonyloxy)-propionic acid methyl ester (40 mg, 0.15 mmol, 0.5 eq.) was added again and the mixture was heated at 90° C. for 4 hours. The mixture was allowed to cool to r.t. and extracted with Et2O (2×), dried over MgSO4, filtered, and concentrated in vacuo. To a solution of the crude ester in THF (1.3 mL), 1M aq. NaOH soln. (0.38 mL) was added. The solution was stirred at r.t. for 18 hours. The solution was diluted with water (2 mL) and 1M aq. HCl soln. (0.38 mL) followed by DCM. The mixture was shaked then the layers were separated and the aq. phase was extracted with DCM (2×). The comb. org. phases were concentrated in vacuo. The crude mixture, redissolved in DMF (1.2 mL), was purified by prep. HPLC (column: Atlantis, 19×50 mm, 5 um, UV/MS, acidic conditions) to give the desired acid.

Workup

  1. temperaturethe mixture was heated at 90° C. for 4 hours
  2. temperatureto cool to r.t.
  3. extractionextracted with Et2O (2×)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. addition(0.38 mL) was added
  8. additionThe solution was diluted with water (2 mL) and 1M aq. HCl soln
  9. customthe layers were separated
  10. extractionthe aq. phase was extracted with DCM (2×)
  11. concentrationphases were concentrated in vacuo
  12. dissolutionThe crude mixture, redissolved in DMF (1.2 mL)
  13. customwas purified by prep

Sources & evidence

ORD record
ord-09794b7f4acd4b3aa379e9971a7b4a7e
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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