Triethylamine → HCID 85422575, compound

HRID 2354263Notes

Reaction equation

HRID 2354263 reaction equation
C([Si](C)(C)O[C:7]1[CH:12]=[CH:11][C:10]([C:13]([C:18]2[CH:31]=[CH:30][C:21]([O:22][CH2:23][C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])=[C:20]([CH3:32])[CH:19]=2)([CH2:16][CH3:17])[CH2:14][CH3:15])=[CH:9][C:8]=1[CH3:33])(C)(C)C.C[Mg+].[Br-].[CH3:39]CCC[N+](CCCC)(CCCC)CCCC.[F-].CCN(CC)CC.[O:64](S(C(F)(F)F)(=O)=O)[S:65]([C:68]([F:71])([F:70])[F:69])(=[O:67])=[O:66]>C1COCC1.CCOC(C)=O>[CH2:16]([C:13]([C:10]1[CH:11]=[CH:12][C:7]([O:64][S:65]([C:68]([F:71])([F:70])[F:69])(=[O:67])=[O:66])=[C:8]([CH3:33])[CH:9]=1)([C:18]1[CH:31]=[CH:30][C:21]([O:22][CH2:23][C:24]([OH:29])([CH3:39])[C:25]([CH3:26])([CH3:28])[CH3:27])=[C:20]([CH3:32])[CH:19]=1)[CH2:14][CH3:15])[CH3:17]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 67749Trifluoromethanesulfonic anhydrideHCID 2724141Tetrabutylammonium FluorideHCID 58775972HCID 58775972, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 85422575HCID 85422575, compoundYield 88.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(4-{1-[4-(tert-Butyl-dimethyl-silanyloxy)-3-methyl-phenyl]-1-ethyl-propyl}-2-methyl-phenoxy)-3,3-dimethyl-butan-2-one (5.63 g, 11.40 mmol) in THF (100 mL) is treated with 3.0 M CH3MgBr (5.7 mL, 17.24 mmol). The reaction is stirred for 1 h, quenched with satd NH4Cl (50 mL) at 0° C., diluted with EtOAc (100 mL), washed with 0.1 M HCl (2×50 mL), MgSO4 dried, and concentrated. The resulting residue is dissolved in THF (50 mL), and reacted with 1.0 M TBAF (12.6 mL, 12.6 mmol) for 1 h. The reaction is diluted with EtOAc (100 mL), washed with 0.1 M HCl (3×50 mL), brine (50 mL), MgSO4 dried, and concentrated. The resulting residue is dissolved in CH2Cl2 (100 mL), cooled to 0° C., treated with Et3N (1.7 mL, 12.38 mmol) and Tf2O (1.9 mL, 11.35 mmol). After stirring 5 m, the reaction is washed with 0.1 M HCl (2×50 mL), MgSO4 dried, concentrated, and chromatographed to give the title compound (5.30 g, 10.0 mmol, 87% for 3-steps). 1H NMR (CDCl3), δ 0.61 (t, J=7.1 Hz, 6H), 1.05(s, 9H), 1.34 (s, 3H), 2.05(q, J=7.1 Hz, 4H), 2.21 (s, 3H), 2.33 (s, 3H), 3.84 (d, J=8.9 Hz, 1H), 4.01 (d, J=8.9 Hz, 1H), 6.71 (d, J=8.3 Hz, 1H), 6.87 (d, J=2.2 Hz, 1H), 6.93 (dd, J=8.8, 2.6 Hz, 1H), 7.02-7.11 (m, 3H). LC/MS (m/z): calcd for C27H41NF3O5S (M+NH4)+: 548.7; found: 548.2.

Workup

  1. customquenched with satd NH4Cl (50 mL) at 0° C.
  2. additiondiluted with EtOAc (100 mL)
  3. washwashed with 0.1 M HCl (2×50 mL), MgSO4
  4. customdried
  5. concentrationconcentrated
  6. dissolutionThe resulting residue is dissolved in THF (50 mL)
  7. washwashed with 0.1 M HCl (3×50 mL), brine (50 mL), MgSO4
  8. customdried
  9. concentrationconcentrated
  10. dissolutionThe resulting residue is dissolved in CH2Cl2 (100 mL)
  11. stirringAfter stirring 5 m
  12. washthe reaction is washed with 0.1 M HCl (2×50 mL), MgSO4
  13. customdried
  14. concentrationconcentrated
  15. customchromatographed

Sources & evidence

ORD record
ord-cf72f35fed7f42d0bf1c9aafe71e4f02
Source dataset
uspto-grants-2010_07
Patent number
US07750184B2

Reaction notes

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