Water → 1-Diphenylmethyl-3-(2,8-bis(trifluoromethyl)-4-quinolinyl)-3-azetidinol

HRID 396356Notes

Reaction equation

HRID 396356 reaction equation
Br[C:2]1[C:11]2[C:6](=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:16]([F:19])([F:18])[F:17])[CH:3]=1.C([Li])CCC.[C:25]1([CH:31]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[N:32]2[CH2:35][C:34](=[O:36])[CH2:33]2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O>CCOCC>[C:37]1([CH:31]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:32]2[CH2:35][C:34]([C:2]3[C:11]4[C:6](=[C:7]([C:12]([F:15])([F:14])[F:13])[CH:8]=[CH:9][CH:10]=4)[N:5]=[C:4]([C:16]([F:19])([F:18])[F:17])[CH:3]=3)([OH:36])[CH2:33]2)[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

6

Reactant 4

HCID 962WaterHCID 37355581-(Diphenylmethyl)azetidin-3-oneHCID 40712424-Bromo-2,8-bis(trifluoromethyl)quinolineHCID 178418339Butyllithium

Product 1

HCID 543985001-Diphenylmethyl-3-(2,8-bis(trifluoromethyl)-4-quinolinyl)-3-azetidinolYield 101.3%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of 4-bromo-2,8-bis(trifluoromethyl)quinoline (500 mg, 1.45 mmol) in dry ether (10 mL) at −78° C. under argon was added n-butyllithium (0.64 mL of 2.5-M, 1.6 mmol). After 20 min a solution of N-diphenylmethyl-3-azetidinone (345 mg, 1.45 mmol) in ether (5 mL) was added dropwise, the mixture stirred for 20 min, water was added and the mixture allowed to warm slowly to room temperature. The mixture was extracted with ether (3×20 mL), the combined extracts dried (MgSO4), concentrated in vacuo and the residue purified by chromatography [SiO2; heptane-EtOAc (3:1)] to give the product (738 mg, 100%) as a pale yellow foam: IR νmax (Nujol)/cm−1 3378, 2924, 1456, 1377, 1311, 1145 and 702; NMR δH (400 MHz, CDCl3) 3.74-3.79 (4H, m), 4.45 (1H, s), 7.21-7.37 (6H, m), 7.41-7.46 (4H, m), 7.65-7.69 (2H, m), 8.15 (1H, d, J 7.1 Hz) and 8.35 (1H, d, J 8.6 Hz).

Workup

  1. extractionThe mixture was extracted with ether (3×20 mL)
  2. dry with materialthe combined extracts dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customthe residue purified by chromatography [SiO2; heptane-EtOAc (3:1)]

Sources & evidence

ORD record
ord-20e67915cca240e790e12836350ba70b
Source dataset
uspto-grants-2003_08
Patent number
US06608085B1

Reaction notes

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