Dimethyl Sulfoxide → 2-(3-{[2,2-Difluoro-2-(4-fluoronaphthyl)ethyl]amino]-6-chloro-2-fluorophenyl)ethanal

HRID 1060224Notes

Reaction equation

HRID 1060224 reaction equation
CS(C)=O.CCN(C(C)C)C(C)C.[F:14][C:15]([F:40])([C:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32]([F:39])=[CH:31][CH:30]=1)[CH2:16][NH:17][C:18]1[C:19]([F:28])=[C:20]([CH2:25][CH2:26][OH:27])[C:21]([Cl:24])=[CH:22][CH:23]=1>C(Cl)Cl>[F:40][C:15]([F:14])([C:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:32]([F:39])=[CH:31][CH:30]=1)[CH2:16][NH:17][C:18]1[C:19]([F:28])=[C:20]([CH2:25][CH:26]=[O:27])[C:21]([Cl:24])=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 81531DiisopropylethylamineHCID 224753262-(3-{[2,2-Difluoro-2-(4-fluoronaphthyl)ethyl]amino]-6-chloro-2-fluorophenyl)ethanol

Product 1

HCID 224753322-(3-{[2,2-Difluoro-2-(4-fluoronaphthyl)ethyl]amino]-6-chloro-2-fluorophenyl)ethanalYield 100.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of DMSO (470 mg, 6.0 mmol), DIEA (823 μL, 4.74 mmol) and 2-(3-{[2,2-difluoro-2-(4-fluoronaphthyl)ethyl]amino}-6-chloro-2-fluorophenyl)ethanol (723 mg, 1.82 mmol), as prepared in the preceding step, in DCM (55 mL) in an ice-bath was added sulfur trioxide pyridine complex (754 mg, 4.74 mmol). After stirring for 3.5 hours the reaction mixture was diluted with DCM (110 mL). The organic layer was separated, and the aqueous layer extracted with DCM (100 mL). The organic layers were combined, washed with 10% citric acid (3 times), H2O, and brine, dried over Na2SO4, and concentrated to give the title compound (722 mg, quantitative yield) as an orange oil. 1H-NMR (400 MHz, CDCl3) δ 9.69 (d, J=1.1 Hz, 1H), 8.22-8.18 (m, 2H), 7.67 -7.60 (m, 3H), 7.14 (t, J=9.2 Hz, 1H), 6.94 (d, J=8.8 Hz, 1H), 6.49 (t, J=8.7 Hz, 1H), 4.20 (bs, 1H), 4.00 (dt, J=13.3, 6.7 Hz, 2H), 3.83 (s, 2H).

Workup

  1. additionwas added sulfur trioxide pyridine complex (754 mg, 4.74 mmol)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer extracted with DCM (100 mL)
  4. washwashed with 10% citric acid (3 times), H2O, and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-e5e2537867a941468d1288f47a19b78a
Source dataset
uspto-grants-2003_02
Patent number
US06521663B2

Reaction notes

Loading…