Triphenylphosphine → n-(4-(2,4-Difluorophenoxy)phenyl)-n-(ethanesulfonyl)-2-fluoropyrid-3-ylmethylamine

HRID 392469Notes

Reaction equation

HRID 392469 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[F:17][C:18]1[C:23]([CH2:24]O)=[CH:22][CH:21]=[CH:20][N:19]=1.[F:26][C:27]1[CH:45]=[C:44]([F:46])[CH:43]=[CH:42][C:28]=1[O:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][S:37]([CH2:40][CH3:41])(=[O:39])=[O:38])=[CH:32][CH:31]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[F:26][C:27]1[CH:45]=[C:44]([F:46])[CH:43]=[CH:42][C:28]=1[O:29][C:30]1[CH:31]=[CH:32][C:33]([N:36]([CH2:24][C:23]2[C:18]([F:17])=[N:19][CH:20]=[CH:21][CH:22]=2)[S:37]([CH2:40][CH3:41])(=[O:38])=[O:39])=[CH:34][CH:35]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylate2×HCID 147614612-Fluoro-3-(hydroxymethyl)pyridineHCID 22663741N-(4-(2,4-Difluorophenoxy)phenyl)-N-ethylsulfonylamine

Product 1

HCID 22663790n-(4-(2,4-Difluorophenoxy)phenyl)-n-(ethanesulfonyl)-2-fluoropyrid-3-ylmethylamineYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Di-tert-butyl azodicarboxylate (0.36 g, 1.57 mmol) was added to a suspension of (2-fluoropyridin-3-yl)methanol (10, 0.20 g, 1.57 mmol), N-(4-(2,4-difluorophenoxy)phenyl)-N-ethylsulfonylamine (0.49 g, 1.56 mmol) and polystyrene resin-bound triphenylphosphine (0.52 g, 1.57 mmol, ˜3 mmol/g) in anhydrous tetrahydrofuran (5 mL) at 0° C. under nitrogen. The resulting yellow suspension was warmed to room temperature and stirred for 19 h, after which additional polystyrene resin bound triphenylphosphine (0.52 g, 1.57 mmol, ˜3 mmol/g) and di-tert-butyl azodicarboxylate (0.36 g, 1.57 mmol) were added. This solution was stirred for 24 h after which the suspension was diluted with anhydrous tetrahydrofuran (100 mL) and the solids were removed by vacuum filtration. The filtrate solvent was removed under reduced pressure to provide the crude product as a yellow oil. This oil was purified by medium pressure liquid chromatography on silica gel, eluting with hexanes/ethyl acetate (7:3), to provide a colorless oil. This oil was triturated with hexanes/ethyl acetate (4-5 mL) to give the title compound as a white powder (0.28 g, 53%): mp 110-112° C.; TLC Rf (3:2 hexanes/ethyl acetate)=0.44; 1H NMR (300 MHz) 8.11 (m, 1H), 7.90 (m, 1H), 7.24-7.15 (m, 3H), 7.11-7.03 (m, 1H), 6.98-6.86 (m, 2H), 6.84 (d, J=6.8 Hz, 2H), 4.91 (s, 2H), 3.15-3.07 (q, J=7.4 Hz, 2H), 1.43 (t, J=7.4 Hz, 1H) ppm; 13C NMR (75 MHz) 163.3, 161.3, 160.1, 157.8, 156.5, 153.1, 147.5 (d, J=14.9 Hz), 141.7, 139.1, 133.6, 130.5, 123.8 (d, J=9.7 Hz), 122.1, 119.1 (d, J=29.2 Hz), 117.5, 112.0 (d, J=22.9 Hz), 106.0 (t, J=24.3 Hz), 49.1, 46.0, 8.44 ppm; APCI MS m/z 423 [C20H17F3N2O3S+H]+. Anal. Calcd. for C20H17F3N2O3S: C, 56.87; H, 4.06; N, 6.63. Found: C, 56.90; H, 4.10; N, 6.45.

Workup

  1. additionwere added
  2. stirringThis solution was stirred for 24 h after which the suspension
  3. customthe solids were removed by vacuum filtration
  4. customThe filtrate solvent was removed under reduced pressure
  5. customto provide the crude product as a yellow oil
  6. customThis oil was purified by medium pressure liquid chromatography on silica gel
  7. washeluting with hexanes/ethyl acetate (7:3)
  8. customto provide a colorless oil
  9. customThis oil was triturated with hexanes/ethyl acetate (4-5 mL)

Sources & evidence

ORD record
ord-4f3878dbbdb04b6b862246f729586a38
Source dataset
uspto-grants-2004_10
Patent number
US06800651B2

Reaction notes

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