Carbon tetrabromide → 2'-(Bromomethyl)-4-fluoro-5-isopropyl-2-methoxy-4'-(trifluoromethyl)biphenyl-3-ol

HRID 1028628Notes

Reaction equation

HRID 1028628 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([Br:24])(Br)(Br)Br.[F:25][C:26]1[C:31]([CH:32]([CH3:34])[CH3:33])=[CH:30][C:29]([C:35]2[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][C:36]=2CO)=[C:28]([O:47][CH3:48])[C:27]=1[OH:49]>C(Cl)Cl>[Br:24][CH2:20][C:36]1[CH:37]=[C:38]([C:41]([F:44])([F:42])[F:43])[CH:39]=[CH:40][C:35]=1[C:29]1[CH:30]=[C:31]([CH:32]([CH3:34])[CH3:33])[C:26]([F:25])=[C:27]([OH:49])[C:28]=1[O:47][CH3:48]

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 866034354-Fluoro-2'-(hydroxymethyl)-5-isopropyl-2-methoxy-4'-(trifluoromethyl)biphenyl-3-ol

Product 1

HCID 866034362'-(Bromomethyl)-4-fluoro-5-isopropyl-2-methoxy-4'-(trifluoromethyl)biphenyl-3-ol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of triphenylphosphine (102.8 mg, 0.392 mmol) in dry CH2Cl2 (2 mL) was added by cannula to a stirred solution of carbon tetrabromide (130 mg, 0.392 mmol) and 4-fluoro-2′-(hydroxymethyl)-5-isopropyl-2-methoxy-4′-(trifluoromethyl)biphenyl-3-ol (58.5 mg, 0.163 mmol) in dry CH2Cl2 (2 mL) at 0° C. under N2 and the reaction was stirred at room temperature overnight. The reaction mixture was 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 2′-(bromomethyl)-4-fluoro-5-isopropyl-2-methoxy-4′-(trifluoromethyl)biphenyl-3-ol. Rf=0.55 (20% EtOAc in hexanes). 1H NMR (600 MHz, CDCl3) δ 7.84 (s, 1H), 7.61 (d, J=7.9 Hz, 1H), 7.42 (d, J=8.0 Hz, 1H), 6.69 (d, J=7.8 Hz, 1H), 5.59 (s, 1H), 4.50 (d, J=9.6 Hz, 1H), 4.39 (d, J=9.7 Hz, 1H), 3.47 (s, 3H), 3.29-3.23 (m, 1H), 1.27 (d, J=6.9 Hz, 6H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customto give the crude product
  3. customThis was purified by flash chromatography (Si, 12×160 mm, 0-40% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-41cebcf78bc24598922d3bb1fddce26a
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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