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

HRID 2075377Notes

Reaction equation

HRID 2075377 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].CCN(C(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) (prepared as shown in Scheme 19) was taken up in 50 mL of DCM and chilled to 0° C. DIEA (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 additional 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 over 12 hours. 1H NMR (400 MHz, CDCl3) δ ppm 7.54 (d, J=8.02 Hz, 2 H) 7.35 (d, J=8.02 Hz, 2 H) 5.61 (s, 1 H) 5.59 (d, J=5.87 Hz, 1 H) 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, 3 H) 1.26 (s, 9 H) 0.92-0.97 (m, 9 H) 0.06 (s, 6 H).

Workup

  1. waitAfter an additional 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-a75aaacb358d439ba6b2b39bb8bb90d6
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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