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

HRID 2226984Notes

Reaction equation

HRID 2226984 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 14 (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 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 residue was purified by flash chromatography (40% to 60% EtOAc in hexanes) giving 6.85 g (91%) of the title compound. 1H NMR (CD3COCD3): δ5 7.41 (2H, m), 7.27 (3H, m), 7.09 (3H, m), 4.63 (2H, d), 4.19 (1H, t), 3.95 (1H, t), 3.88 (1H, s), 3.57 (3H, s), 3.1 (1H, ddd), 2.8 (1H, ddd), 2.5 (2H, s), 2.4 (2H, d), 2.17 (2H, m), 1.52 (6H, s), 0.52-0.35 (4H, m).

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-7a941578fc1844a396c8bd40ce0981d4
Source dataset
uspto-grants-1994_09
Patent number
US05350760

Reaction notes

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