Hydrochloric Acid → Ethyl 3-[4-chloro-3-((1S)-1-hydroxy-2-{[(4-methylphenyl)sulfonyl]oxy}ethyl)phenyl]propanoate

HRID 602063Notes

Reaction equation

HRID 602063 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:15][C:14]=1[C@H:26]([OH:29])[CH2:27][OH:28].Cl.C(OCC)C>N1C=CC=CC=1>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:15][C:14]=1[C@H:26]([OH:29])[CH2:27][O:28][S:7]([C:4]1[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=1)(=[O:9])=[O:8]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 73974-Toluenesulfonyl chlorideHCID 57470609Ethyl 3-{4-chloro-3-[(1S)-1,2-dihydroxyethyl]phenyl}propanoate

Product 1

HCID 57470611Ethyl 3-[4-chloro-3-((1S)-1-hydroxy-2-{[(4-methylphenyl)sulfonyl]oxy}ethyl)phenyl]propanoateYield 80.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

p-Toluenesulfonyl chloride (1.08 g, 5.69 mmol) in pyridine (15 mL) was added drop wise over 30 min to a cooled (0° C.) solution of ethyl 3-{4-chloro-3-[(1S)-1,2-dihydroxyethyl]phenyl}propanoate (1.41 g, 5.17 mmol) in pyridine (20 mL) under N2. The solution slowly warmed to rt overnight. After 16 h, 1N HCl and ethyl ether were added. The organic layer was isolated and the aqueous layer washed with ethyl ether (2×). The combined organic fractions were washed with 1N HCl, 10% aqueous Cu2SO4, brine, dried (Na2SO4), and concentrated. The crude product was purified by Biotage chromatography (0%-10% EtOAc/Hexanes) to afford 1.77 g of product as an oil (80%). 1H NMR (400 MHz, chloroform-d) δ ppm 7.81 (d, J=8.08 Hz, 2 H) 7.43 (d, J=2.27 Hz, 1 H) 7.36 (d, J=8.34 Hz, 2 H) 7.22 (d, J=8.08 Hz, 1 H) 7.10 (dd, J=8.21, 1.89 Hz, 1 H) 5.34 (td, J=5.62, 2.91 Hz, 1 H) 4.28 (dd, J=10.61, 2.53 Hz, 1 H) 4.14 (q, J=7.24 Hz, 2 H) 3.98 (dd, J=10.61, 8.34 Hz, 1 H) 2.93 (t, J=7.71 Hz, 2 H) 2.60 (t, J=7.83 Hz, 2 H) 2.47 (s, 3 H) 1.25 (t, J=7.07 Hz, 3 H).

Workup

  1. customThe organic layer was isolated
  2. washthe aqueous layer washed with ethyl ether (2×)
  3. washThe combined organic fractions were washed with 1N HCl, 10% aqueous Cu2SO4, brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude product was purified by Biotage chromatography (0%-10% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-4432368462874557add4bbda7639f598
Source dataset
uspto-grants-2011_03
Patent number
US07902394B2

Reaction notes

Loading…