Ammonium Chloride → 4-Fluoro-2'-(hydroxymethyl)-5-isopropyl-2-methoxy-4'-(trifluoromethyl)biphenyl-3-ol

HRID 1028627Notes

Reaction equation

HRID 1028627 reaction equation
[F-].C([NH3+])(C)(C)C.[Si]([O:14][CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[C:26]1[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[C:29]([F:35])=[C:28]([OH:36])[C:27]=1[O:37][CH3:38])(C(C)(C)C)(C)C.[NH4+].[Cl-]>C1COCC1>[F:35][C:29]1[C:30]([CH:32]([CH3:33])[CH3:34])=[CH:31][C:26]([C:17]2[CH:18]=[CH:19][C:20]([C:22]([F:24])([F:25])[F:23])=[CH:21][C:16]=2[CH2:15][OH:14])=[C:27]([O:37][CH3:38])[C:28]=1[OH:36]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 21866379t-Butylammonium fluorideHCID 866034342'-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-4-fluoro-5-isopropyl-2-methoxy-4'-(trifluoromethyl)biphenyl-3-ol

Product 1

HCID 866034354-Fluoro-2'-(hydroxymethyl)-5-isopropyl-2-methoxy-4'-(trifluoromethyl)biphenyl-3-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butylammonium fluoride (1M in THF, 179 μL, 0.179 mmol) was added dropwise to a stirred solution of 2′-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-fluoro-5-isopropyl-2-methoxy-4′-(trifluoromethyl)biphenyl-3-ol (76.8 mg, 0.163 mmol) in THF (2 mL) at 0° C. and the reaction was allowed to warm to room temperature overnight. Saturated NH4Cl (10 ml) was added and the mixture was extracted with EtOAc (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-40% EtOAc in hexanes gradient) to afford 4-fluoro-2′-(hydroxymethyl)-5-isopropyl-2-methoxy-4′-(trifluoromethyl)biphenyl-3-ol. Rf=0.26 (20% EtOAc in hexanes). 1H NMR (600 MHz, CDCl3) δ 7.85 (s, 1H), 7.63 (d, J=7.9 Hz, 1H), 7.41 (d, J=8.0 Hz, 1H), 6.53 (d, J=7.7 Hz, 1H), 4.50 (br s, 1H), 4.47 (s, 1H), 3.42 (s, 3H), 3.25-3.19 (m, 1H), 1.24 (br s, 6H).

Workup

  1. extractionthe mixture was extracted with EtOAc (3×20 mL)
  2. dry with materialThe combined extracts were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customto give the crude product
  5. customThis was purified by flash chromatography (Si, 12×160 mm, 0-40% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-e6e67e3dd7804e00b0e941911422207e
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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