Diisopropylethylamine → tert-butyl (2S,3S,E)-1-(tert-butyldimethylsilyloxy)-3-(4-(trifluoromethyl)phenyl)hex-4-en-2-ylcarbamate

HRID 2109764Notes

Reaction equation

HRID 2109764 reaction equation
[OH:1][CH2:2][C@@H:3]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C@H:4]([C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1)/[CH:5]=[CH:6]/[CH3:7].C(N(CC)C(C)C)(C)C.FC(F)(F)S(O[Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])(=O)=O>C(Cl)Cl>[Si:41]([O:1][CH2:2][C@@H:3]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C@H:4]([C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1)/[CH:5]=[CH:6]/[CH3:7])([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonate2×HCID 57633996Tert-butyl (2S,3S,E)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)hex-4-en-2-ylcarbamate

Product 1

HCID 86613773tert-butyl (2S,3S,E)-1-(tert-butyldimethylsilyloxy)-3-(4-(trifluoromethyl)phenyl)hex-4-en-2-ylcarbamateYield 78.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Tert-butyl (2S,3S,E)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)hex-4-en-2-ylcarbamate (1.94 g, 5.4 mmol) was taken up in 50 mL of DCM and chilled to 0° C. N,N-diisopropylethylamine (2.4 mL, 13 mmol) was added, followed by slow addition of tert-butyldimethylsilyl trifluoromethanesulfonate (TBSOTf) (1.5 mL, 6.5 mmol). After 45 minutes, an additional 0.20 mL of TBSOTf was added. After an addition 20 minutes, the reaction was quenched with 50 mL of aq NaHCO3. The mixture was partitioned, and the aqueous portion was extracted twice with 50 mL of DCM. The combined organic extracts were dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (1% to 7.5% EtOAc/hexanes) afforded tert-butyl (2S,3S,E)-1-(tert-butyldimethylsilyloxy)-3-(4-(trifluoromethyl)phenyl)hex-4-en-2-ylcarbamate (2.0 g, 78% yield) as a clear oil. The oil crystallized on the bench top over 12 hours. 1H NMR (400 MHz, CDCl3) δ ppm 7.54 (d, J=8.02 Hz, 2H) 7.35 (d, J=8.02 Hz, 2H) 5.61 (s, 1H) 5.59 (d, J=5.87 Hz, 1H) 4.62-4.60 (m, 1H) 3.97-3.92 (m, 1H) 3.79-3.76 (m, 1H) 3.66-3.59 (m, 2H) 1.69 (d, J=5.28 Hz, 3H) 1.26 (s, 9H) 0.92-0.97 (m, 9H) 0.06 (s, 6H).

Workup

  1. additionAfter an addition 20 minutes
  2. customthe reaction was quenched with 50 mL of aq NaHCO3
  3. customThe mixture was partitioned
  4. extractionthe aqueous portion was extracted twice with 50 mL of DCM
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-b9820704d9c04f58ab5f6d65e4004ace
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

Loading…