p-Toluenesulfonic acid monohydrate → methyl 4-{(1S)-1-[({2,5-dichloro-4-[(3-chlorophenyl)(hydroxy)methyl]-3-thienyl}carbonyl)amino]ethyl}benzoate

HRID 870052Notes

Reaction equation

HRID 870052 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Cl:13][C:14]1[S:15][C:16]([Cl:49])=[C:17]([CH:34]([C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([Cl:48])[CH:43]=2)[O:35]C2CCCCO2)[C:18]=1[C:19]([NH:21][C@H:22]([C:24]1[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=1)[CH3:23])=[O:20]>CO>[Cl:13][C:14]1[S:15][C:16]([Cl:49])=[C:17]([CH:34]([C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([Cl:48])[CH:43]=2)[OH:35])[C:18]=1[C:19]([NH:21][C@H:22]([C:24]1[CH:25]=[CH:26][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:32][CH:33]=1)[CH3:23])=[O:20]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 57900986methyl 4-{(1S)-1-[({2,5-dichloro-4-[(3-chlorophenyl)(tetrahydro-2H-pyran-2-yloxy)methyl]-3-thienyl}carbonyl)amino]ethyl}benzoate

Product 1

HCID 57900983methyl 4-{(1S)-1-[({2,5-dichloro-4-[(3-chlorophenyl)(hydroxy)methyl]-3-thienyl}carbonyl)amino]ethyl}benzoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

p-Toluenesulfonic acid monohydrate (6.00 mg, 0.0338 mmol) was added to methyl 4-{(1S)-1-[({2,5-dichloro-4-[(3-chlorophenyl)(tetrahydro-2H-pyran-2-yloxy)methyl]-3-thienyl}carbonyl)amino]ethyl}benzoate from Example 8, Step 4 (197 mg, 0.338 mmol) in MeOH (2 mL). After 1.5 h, the reaction mixture was quenched with 5% aq. NaHCO3 and extracted with EtOAc. The combined organics were washed with 5% aq. NaHCO3, water and brine, dried (Na2SO4) and concentrated. The crude product was purified by Combi Flash chromatography system (2-8% EtOAc/toluene in 20 min.) to afford the desired product as a colorless gum.

Workup

  1. customthe reaction mixture was quenched with 5% aq. NaHCO3
  2. extractionextracted with EtOAc
  3. washThe combined organics were washed with 5% aq. NaHCO3, water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude product was purified by Combi Flash chromatography system (2-8% EtOAc/toluene in 20 min.)

Sources & evidence

ORD record
ord-6ab8bdd7378b4b26a87d3f073a922f2d
Source dataset
uspto-grants-2015_03
Patent number
US08969394B2

Reaction notes

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