Triphenylphosphine → 2-(Bromomethyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridine

HRID 1496924Notes

Reaction equation

HRID 1496924 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:14]=[CH:15][C:16]([CH2:19]O)=[N:17][CH:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:11])[F:10].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Br:40]N1C(=O)CCC1=O>C(Cl)Cl>[Br:40][CH2:19][C:16]1[CH:15]=[CH:14][C:13]([C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]([F:12])([F:11])[F:10])=[C:2]([F:1])[CH:3]=2)=[CH:18][N:17]=1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 49852040{5-[3-Fluoro-4-(trifluoromethoxy)phenyl]-2-pyridinyl}methanol

Product 1

HCID 498520412-(Bromomethyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridineYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of alcohol 106 (678 mg, 2.36 mmol) and triphenylphosphine (746 mg, 2.84 mmol) in anhydrous CH2Cl2 (30 mL) was carefully treated with recrystallized N-bromosuccinimide (507 mg, 2.85 mmol) (water bath cooling), and the mixture was stirred at room temperature for 3 h. The resulting solution was concentrated, and then added to excess petroleum ether at the top of a silica gel column (25 g in petroleum ether), rinsing on with minimal extra CH2Cl2. Elution with petroleum ether firstly gave foreruns, and then further elution with 10-20% Et2O/pentane gave 2-(bromomethyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]pyridine (107) (616 mg, 75%) as a white solid that was used directly in the next step; 1H NMR (CDCl3) δ 8.76 (dd, J=2.4, 0.6 Hz, 1H), 7.84 (dd, J=8.1, 2.4 Hz, 1H), 7.54 (dd, J=8.0, 0.6 Hz, 1H), 7.46-7.33 (m, 3H), 4.60 (s, 2H); HRESIMS calcd for C13H9BrE4NO m/z [M+H]+ 351.9778, 349.9798, found 351.9778, 349.9798.

Workup

  1. concentrationThe resulting solution was concentrated
  2. additionadded to excess petroleum ether at the top of a silica gel column (25 g in petroleum ether)
  3. washrinsing on with minimal extra CH2Cl2
  4. washElution with petroleum ether firstly gave foreruns
  5. washfurther elution with 10-20% Et2O/pentane

Sources & evidence

ORD record
ord-3bd841b0d3994fb6a6f2af6c182c1a68
Source dataset
uspto-grants-2015_12
Patent number
US09198913B2

Reaction notes

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