(Diethylamino)sulfur trifluoride → (S)-2-((R)-1-Fluoro-2-morpholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid methyl ester

HRID 1830158Notes

Reaction equation

HRID 1830158 reaction equation
C(N(S(F)(F)[F:7])CC)C.[CH3:10][O:11][C:12](=[O:33])[C@@H:13]([C@H:23](O)[C:24]([N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)=[O:25])[CH2:14][CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(Cl)Cl>[CH3:10][O:11][C:12](=[O:33])[C@@H:13]([C@@H:23]([F:7])[C:24]([N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)=[O:25])[CH2:14][CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 69434738(R)-2-((S)-1-Hydroxy-2-morpholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid methyl ester

Product 1

HCID 69434202(S)-2-((R)-1-Fluoro-2-morpholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid methyl esterYield 27.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(Diethylamino) sulfur trifluoride (2.0 ml, 15.2 mmol) was added to a ice cold solution of (R)-2-((S)-1-Hydroxy-2-morpholin-4-yl-2-oxo-ethyl)-5-phenyl-pentanoic acid methyl ester (4a) (0.85 g, 2.5 mmol) in dry methylene chloride (15 ml) and the reaction mixture was stirred overnight while warming to room temperature. The reaction was quenched with aqueous NaHCO3 solution and extracted with methylene chloride. The organic extracts were dried over Na2SO4 and concentrated under reduced pressure. Column chromatography on silica eluting with a mixture of ethyl acetate and methylene chloride gave the title compound as an off-white solid (230 mg). 1H NMR (CDCl3) δ 1.90–1.58 (m, 4H), 2.78–2.57 (m, 2H), 3.28–3.10 (m, 1H), 3.75 (s, 3H), 3.74–3.45 (m, 8H), 5.40–5.12 (m, 1H), 7.35–7.18 (m, 5H); MS: 338(MH+).

Workup

  1. customThe reaction was quenched with aqueous NaHCO3 solution
  2. extractionextracted with methylene chloride
  3. dry with materialThe organic extracts were dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. additionColumn chromatography on silica eluting with a mixture of ethyl acetate and methylene chloride

Sources & evidence

ORD record
ord-4a4e2630230a40f7a6bd3e5d2e9481d1
Source dataset
uspto-grants-2006_06
Patent number
US07064123B1

Reaction notes

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