Trichloroethanol → 3-[4-(Tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid 2,2,2-trichloro-ethyl ester

HRID 1628139Notes

Reaction equation

HRID 1628139 reaction equation
[C:1]([SiH2:5][O:6][C:7]([CH3:30])([CH3:29])[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH:15]([S:19][CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[C:16]([OH:18])=[O:17])=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:31][C:32]([Cl:36])([Cl:35])[CH2:33]O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:31][C:32]([Cl:36])([Cl:35])[CH2:33][O:17][C:16](=[O:18])[CH:15]([S:19][CH2:20][CH2:21][C:22]1[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=1)[CH2:14][C:11]1[CH:10]=[CH:9][C:8]([C:7]([CH3:30])([CH3:29])[O:6][SiH2:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:13][CH:12]=1

Participants

5

Reactant 2

HCID 8259TrichloroethanolHCID 1317316793-[4-(tert-Butyl-dimethyl-silanyloxymethyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid

Product 1

HCID 1317316803-[4-(Tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid 2,2,2-trichloro-ethyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-[4-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid (4.79 g, 10.68 mmol) and 2,2,2-trichloroethanol (1.67 g, 11.22 mmol) in anhydrous DCM (300 mL) was first added EDCxHCl (2.66 g, 13.89 mmol) then DMAP (13 mg, 0.1 mmol) under nitrogen atmosphere at 0° C. After complete addition the cooling bath was removed and the reaction mixture was stirred at ambient temperature until no starting material was left. The mixture was diluted with water and aq. HCl (2N) and extracted with DCM. The combined organic layers were dried (MgSO4) and the solvent was evaporated under reduced pressure to afford the crude product which was directly proceeded to the next step (5.47 g, 88.3%). 1H NMR (400 MHz, CDCl3): δ 7.16 (t, 2H), 7.10 (d, 2H), 7.01 (t, 2H), 6.87 (t, 2H), 4.61 (q, 4H), 3.48 (dd, 1H), 3.12 (dd, 1H), 2.73-2.89 (m, 5H), 0.85 (s, 9H), 0.00 (s, 6H). Mass Spectrum: M−H+ 579.03.

Workup

  1. customat 0° C
  2. additionAfter complete addition the cooling bath
  3. customwas removed
  4. waitwas left
  5. additionThe mixture was diluted with water and aq. HCl (2N)
  6. extractionextracted with DCM
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-6f1ef97c43314b43a3c332019ad8f11d
Source dataset
uspto-grants-2014_07
Patent number
US08785681B2

Reaction notes

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