Pyridine → (R)Methyl 1-(((1-(3-(hydroxymethyl)phenyl)-3-(2-(2-hydroxy-2-propyl)phenyl)propyl)thio)methyl)cyclopropaneacetate

HRID 1720363Notes

Reaction equation

HRID 1720363 reaction equation
[OH:1][C:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][CH2:12][C@@H:13]([S:28][CH2:29][C:30]1([CH2:33][C:34]([O:36][CH3:37])=[O:35])[CH2:32][CH2:31]1)[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][O:21]C2CCCCO2)[CH:15]=1)([CH3:4])[CH3:3].N1C=CC=CC=1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>CO>[OH:21][CH2:20][C:16]1[CH:15]=[C:14]([C@H:13]([S:28][CH2:29][C:30]2([CH2:33][C:34]([O:36][CH3:37])=[O:35])[CH2:32][CH2:31]2)[CH2:12][CH2:11][C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:2]([OH:1])([CH3:4])[CH3:3])[CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 18655247Methyl 1-(((1(R)-(3-(((2-tetrahydropyranyl)oxy)methyl)phenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropaneacetate

Product 1

HCID 18655248(R)Methyl 1-(((1-(3-(hydroxymethyl)phenyl)-3-(2-(2-hydroxy-2-propyl)phenyl)propyl)thio)methyl)cyclopropaneacetateYield 91%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
55 °C

Procedure

To the hydroxy ester from Step 16 (9.02 g, 17.1 mmol) in anhydrous methanol (60 mL) under nitrogen was added pyridine (50 μL) followed by pyridinium p-toluenesulfonate (1.1 g, 4.3 mmol). The reaction mixture was stirred 3.5 hours at 55° C., then at r.t. overnight before concentrating in vacuo. The residue was diluted with EtOAc (500 mL) and washed with H2O, saturated aq. NaHCO3, NaH2PO4 buffer (pH=4.5) and with brine. After drying over MgSO4 and evaporation of the solvents, the product was purified by flash chromatography (40% to 60% EtOAc in hexanes) giving 6.85 g (91%) of the title compound.

Workup

  1. concentrationat r.t. overnight before concentrating in vacuo
  2. additionThe residue was diluted with EtOAc (500 mL)
  3. washwashed with H2O, saturated aq. NaHCO3, NaH2PO4 buffer (pH=4.5) and with brine
  4. dry with materialAfter drying over MgSO4 and evaporation of the solvents
  5. customthe product was purified by flash chromatography (40% to 60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-483cc70a959a46d582174de99f661ef3
Source dataset
uspto-grants-1996_04
Patent number
US05506227

Reaction notes

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