Triphenylphosphine → Ethyl (S)-4-[4-[2-[6-(methylamino)pyridin-2-yl]ethoxy]phenyl]-3-(pyridin-3-yl)butanoate

HRID 1816017Notes

Reaction equation

HRID 1816017 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[OH:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C@H:23]([C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)[CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:18][CH:17]=1.[CH3:36][NH:37][C:38]1[N:43]=[C:42]([CH:44](O)[CH3:45])[CH:41]=[CH:40][CH:39]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[CH3:36][NH:37][C:38]1[N:43]=[C:42]([CH2:44][CH2:45][O:15][C:16]2[CH:17]=[CH:18][C:19]([CH2:22][C@H:23]([C:30]3[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=3)[CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:20][CH:21]=2)[CH:41]=[CH:40][CH:39]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 223194656-(Methylamino)-2-pyridylethanolHCID 59997616ethyl (S)-4-(4-hydroxyphenyl)-3-(pyridin-3-yl)butanoate

Product 1

HCID 59997613Ethyl (S)-4-[4-[2-[6-(methylamino)pyridin-2-yl]ethoxy]phenyl]-3-(pyridin-3-yl)butanoateYield 66.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diisopropyl azodicarboxylate (7.8 mL, 39.8 mmole) was added dropwise to a solution of ethyl (S)-4-(4-hydroxyphenyl)-3-(pyridin-3-yl)butanoate (9.455 g, 33.1 mmole), 6-(methylamino)-2-pyridylethanol (6.06 g, 39.8 mmole), and triphenylphosphine (10.44 g, 39.8 mmole) in anhydrous THF (150 mL) at 0° C. The mixture was allowed to warm to RT as the bath warmed. After 18 hr the reaction was concentrated and the residue was flash chromatographed on silica gel (3% MeOH in 1:1 EtOAc/CHCl3) to afford the title compound (9.2 g, 66%) as a viscous yellow oil: 1H NMR (400 MHz, CDCl3) δ 8.43 (dd, J=4.8, 1.6 Hz, 1 H). 8.39 (d, J=1.9 Hz, 1 H), 7.31-7.45 (m, 2 H), 7.13-7.21 (m, 1 H), 6.91 (d, J=8.6 Hz, 2 H), 6.77 (d, 3=8.6 Hz, 2 H), 6.53 (d, J=7.3 Hz, 1 H), 6.24 (d, J=8.2 Hz, 1 H), 4.43-4.58 (m, 1 H), 4.26 (t, J=7.0 Hz, 2 H), 3.92-4.05 (m, 2 H), 3.32-3.45 (m, 1 H), 3.04 (t, J=7.0 Hz, 2 H), 2.89 (d, J=5.3 Hz, 3 H), 2.88 (dd, J=13.7, 7.2 Hz, 1 H), 2.82 (dd, J=13.7, 7.8 Hz, 1 H), 2.70 (dd, J=15.6, 6.3 Hz, 1 H), 2.59 (dd, J=15.6, 9.0 Hz, 1 H), 1.11 (t, J=7.1 Hz, 3 H); MS (ES) m/e 420 (M+H)+.

Workup

  1. temperaturewarmed
  2. concentrationAfter 18 hr the reaction was concentrated
  3. customchromatographed on silica gel (3% MeOH in 1:1 EtOAc/CHCl3)

Sources & evidence

ORD record
ord-bd9c2d131f1b4bd7a2c6d589e44da348
Source dataset
uspto-grants-2005_04
Patent number
US06881736B1

Reaction notes

Loading…