Triphenylphosphine → 1-tert-butyl 2-[2-(trimethylsilyl)ethyl] (2S,4R)-4-[(2-phenyl-6-vinylquinolin-4-yl)oxy]pyrrolidine-1,2-dicarboxylate

HRID 1360094Notes

Reaction equation

HRID 1360094 reaction equation
[OH:1][C@@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])=[O:15])[CH2:3]1.[C:23]1([C:29]2[NH:30][C:31]3[C:36]([C:37](=O)[CH:38]=2)=[CH:35][C:34]([CH:40]=[CH2:41])=[CH:33][CH:32]=3)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:23]1([C:29]2[CH:38]=[C:37]([O:1][C@H:2]3[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:12])([CH3:13])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])=[O:15])[CH2:3]3)[C:36]3[C:31](=[CH:32][CH:33]=[C:34]([CH:40]=[CH2:41])[CH:35]=3)[N:30]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 5462977Diethyl azodicarboxylate2×HCID 576171082-phenyl-6-vinylquinolin-4(1H)-oneHCID 576171281-tert-butyl 2-[2-(trimethylsilyl)ethyl] (2S,4S)-4-hydroxypyrrolidine-1,2-dicarboxylate

Product 1

HCID 576171271-tert-butyl 2-[2-(trimethylsilyl)ethyl] (2S,4R)-4-[(2-phenyl-6-vinylquinolin-4-yl)oxy]pyrrolidine-1,2-dicarboxylateYield 50.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-tert-butyl 2-[2-(trimethylsilyl)ethyl] (2S,4S)-4-hydroxypyrrolidine-1,2-dicarboxylate 3 (1.0 g, 3.02 mmol) in THF (30 mL) was added 2-phenyl-6-vinylquinolin-4(1H)-one 2 (0.78 g, 3.17 mmol) and PPh3 (1.19 g, 4.52 mmol). The flask was then cooled to 0° C. and diethylazodicarboxylate (0.713 mL, 4.52 mmol) was added slowly. The mixture was then warmed to RT and stirred overnight (16 h). At this time, the starting material to product ratio was 2:1. The reaction was re-cooled to 0° C., and additional PPh3 (1.19 g, 4.52 mmol) and diethylazodicarboxylate (0.713 mL, 4.52 mmol) were added. After stirring for an additional 19 h, only a small amount of starting material remained. Silica gel was then added to the reaction and the mixture was filtered through silica gel with EtOAc as the eluent. The crude mixture was then purified on silica (5-40% EtOAc/hexanes) to yield 0.85 g (50% yield) of 1-tert-butyl 2-[2-(trimethylsilyl)ethyl] (2S,4R)-4-[(2-phenyl-6-vinylquinolin-4-yl)oxy]pyrrolidine-1,2-dicarboxylate 5. 1H NMR (500 MHz, CDCl3) ppm: mixture of amide rotamers: 8.43 (m, 1H), 8.13-8.09 (m, 2H), 7.92 and 7.91 (2 br s, 2H), 7.56 (m, 3H), 7.12 and 7.11 (2 br s, 1H), 6.92 (br dd, J=17.5 Hz, 10.5 Hz, 1H), 6.02 (d, J=17.5 Hz, 1H), 5.58 (d, J=10.5 Hz, 1H), 5.53 and 5.49 (2 br s, 1H), 4.64 and 4.54 (2 app t, J=7.5 Hz, 1H), 4.27 (app t, J=7 Hz, 2H), 4.07 (m, 1.5H), 3.89 (br d, J=13 Hz, 0.5H), 2.81 (m, 1H), 2.55 (m, 1H), 1.47 and 1.45 (2 s, 9H), 1.04 (m, 2H), 0.07 and 0.06 (2 s, 9H). LRMS (CI, [M+H]) Calc'd=561.4. found=561.4. HRMS (APCI, [M+H]+) Calc'd for C32H41N2O5Si: 561.2779. found: 561.2749.

Workup

  1. temperatureThe mixture was then warmed to RT
  2. temperatureThe reaction was re-cooled to 0° C.
  3. stirringAfter stirring for an additional 19 h
  4. additionSilica gel was then added to the reaction
  5. filtrationthe mixture was filtered through silica gel with EtOAc as the eluent
  6. customThe crude mixture was then purified on silica (5-40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-785b08fdf0ee415ebd659854baa1f9a9
Source dataset
uspto-grants-2011_02
Patent number
US07879797B2

Reaction notes

Loading…