Triethylamine → HCID 86707792, compound

HRID 2174368Notes

Reaction equation

HRID 2174368 reaction equation
[FH:1].F.F.C(N(CC)CC)C.C(N(CC)CC)C.[CH2:18]([O:20][C:21]([CH:23]1[CH2:26][C:25](O)([C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH2:37][C:36]([C:42]4[CH:47]=[C:46]([Cl:48])[C:45]([Cl:49])=[C:44]([Cl:50])[CH:43]=4)([C:38]([F:41])([F:40])[F:39])[O:35][N:34]=3)=[CH:29][CH:28]=2)[CH2:24]1)=[O:22])[CH3:19]>C(Cl)Cl>[CH2:18]([O:20][C:21]([CH:23]1[CH2:24][C:25]([F:1])([C:27]2[CH:32]=[CH:31][C:30]([C:33]3[CH2:37][C:36]([C:42]4[CH:43]=[C:44]([Cl:50])[C:45]([Cl:49])=[C:46]([Cl:48])[CH:47]=4)([C:38]([F:40])([F:41])[F:39])[O:35][N:34]=3)=[CH:29][CH:28]=2)[CH2:26]1)=[O:22])[CH3:19]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 175505N,N-Diethylethanamine trihydrofluorideHCID 86707790HCID 86707790, compound

Product 1

HCID 86707792HCID 86707792, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of triethyl amine trihydrofluoride (4.21 g, 26.16 mmol, 4 eq.) in DCM (25 mL) was added triethyl amine (1.32 g, 13.08 mmol) in drop wise manner at −78° C. After 15 minutes was added X-TalFluoro-M (4.74 g, 19.62 mmol) followed by addition of pre-dissolved solution of 3-hydroxy-3-{4-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-phenyl}-cyclobutanecarboxylic acid ethyl ester (Preparation 3, 3.5 g, 6.54 mmol) in DCM (15 mL) at −78° C. Resulting reaction mixture was stirred at room temperature for 16 hours. After consumption of starting material, reaction mixture was quenched with saturated aqueous solution of sodium bicarbonate (50 mL) and stirred at room temperature for 0.5 hours. Aqueous layer was extracted with DCM (3×50 mL). Combined organic layers were dried over sodium sulphate, filtered and evaporated. Purification was done by column chromatography on silica gel (100-200 mesh size). Compounds were eluted using 5% ethyl acetate in hexane to afford two off-white solids (2 g-non-polar spot, and 1.2 g-polar spot). 1H NMR (400 MHz, CDCl3) (Non Polar spot) δ: 1.26 (t, J=7.12 Hz, 3H), 2.80 (d, J=8.76 Hz, 2H), 2.87 (d, J=8.72 Hz, 2H), 3.47-3.49 (m, 1H), 3.67 (d, J=17.16 Hz, 1H), 4.08 (d, J=17.16 Hz, 1H), 4.16 (q, J=7.2 Hz, 2H), 7.51 (d, J=8.12 Hz, 2H), 7.63 (s, 2H), 7.67 (d, J=8.16 Hz, 2H); LC-MS (m/z): 536.00 (M−H).

Workup

  1. additionAfter 15 minutes was added X-TalFluoro-M (4.74 g, 19.62 mmol)
  2. customResulting
  3. customreaction mixture
  4. customAfter consumption of starting material, reaction mixture
  5. customwas quenched with saturated aqueous solution of sodium bicarbonate (50 mL)
  6. stirringstirred at room temperature for 0.5 hours
  7. extractionAqueous layer was extracted with DCM (3×50 mL)
  8. dry with materialCombined organic layers were dried over sodium sulphate
  9. filtrationfiltered
  10. customevaporated
  11. customPurification
  12. washCompounds were eluted
  13. customto afford two off-white solids (2 g-non-polar spot, and 1.2 g-polar spot)

Sources & evidence

ORD record
ord-2eb39b5b8ff1450abb2c8d6496f00c50
Source dataset
uspto-grants-2015_06
Patent number
US09061013B2

Reaction notes

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