Tetrabutylammonium Fluoride → HCID 23582677, compound

HRID 238758Notes

Reaction equation

HRID 238758 reaction equation
[Si]([O:18][C:19]1[CH:20]=[C:21]([C@:26]([NH:45][C:46]([NH:48][CH2:49][C:50]([F:53])([F:52])[F:51])=[O:47])([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[C:36]([C:41]([F:44])([F:43])[F:42])[CH:35]=2)[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:22]=[C:23]([F:25])[CH:24]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.C(Cl)Cl>[F:40][C:37]1[CH:38]=[CH:39][C:34]([C@@:26]([NH:45][C:46]([NH:48][CH2:49][C:50]([F:51])([F:52])[F:53])=[O:47])([C:21]2[CH:20]=[C:19]([OH:18])[CH:24]=[C:23]([F:25])[CH:22]=2)[CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:35][C:36]=1[C:41]([F:44])([F:42])[F:43]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 59459424HCID 59459424, compound

Product 1

HCID 23582677HCID 23582677, compoundYield 78.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-1-(1-(3-(tert-butyldiphenylsilyloxy)-5-fluorophenyl)-1-(4-fluoro-3-(trifluoromethyl)phenyl)-2-phenylethyl)-3-(2,2,2-trifluoroethyl)urea (85 mg, 0.11 mmol) in THF (1.5 mL) was added TBAF (1.0 M in THF, 0.12 mL, 0.12 mmol). The resulting mixture was stirred at room temperature for 45 min. The reaction was diluted with CH2Cl2 and washed with sat. NH4Cl, H2O and sat. NaCl, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by flash chromatography (silica gel, hexanes/EtOAc) to give (R)-1-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-hydroxyphenyl)-2-phenylethyl)-3-(2,2,2-trifluoroethyl)urea (Example 254, 45 mg, yield 77%). LCMS: RT=2.0 min [M+H] 519.1 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm). 1H NMR (400 MHz, CDCl3) δ ppm 7.20-7.27 (3H, m), 7.09-7.18 (3H, m), 6.72 (1H, d, J=9.60 Hz), 6.66 (3H, d, J=7.07 Hz), 6.57 (1H, s), 3.73-3.78 (1H, m), 3.65-3.71 (1H, m), 3.63 (1H, d, J=8.59 Hz), 3.47-3.58 (1H, m).

Workup

  1. washwashed with sat. NH4Cl, H2O and sat. NaCl
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue was purified by flash chromatography (silica gel, hexanes/EtOAc)

Sources & evidence

ORD record
ord-60181e8e7a9c4cd59c787891f0b5a4fa
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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