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

HRID 2259493Notes

Reaction equation

HRID 2259493 reaction equation
O1CCCCC1[O:7][CH2:8][C:9]1[CH:10]=[C:11]([C@H:15]([S:28][CH2:29][C:30]2([CH2:33][C:34]([O:36][CH3:37])=[O:35])[CH2:32][CH2:31]2)[CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]([OH:27])([CH3:26])[CH3:25])[CH:12]=[CH:13][CH:14]=1.N1C=CC=CC=1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>CO>[OH:7][CH2:8][C:9]1[CH:10]=[C:11]([C@H:15]([S:28][CH2:29][C:30]2([CH2:33][C:34]([O:36][CH3:37])=[O:35])[CH2:32][CH2:31]2)[CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]([OH:27])([CH3:26])[CH3:25])[CH:12]=[CH:13][CH:14]=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 15 (9.02 g, 17.1 mol) in anhydrous MeOH (60 mL) under nitrogen was added pyridine (50 μL) followed by PPTS (1.1 g, 4.3 mmol). The reaction mixture was stirred 3.5 hr 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 residue 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 residue was purified by flash chromatography (40% to 60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-e7df4bf8f2b24defac479af0420aa362
Source dataset
uspto-grants-1995_12
Patent number
US05472964

Reaction notes

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