Reference:
[1] Organic Preparations and Procedures International, 2007, vol. 39, # 5, p. 514 - 517
[2] Organic Preparations and Procedures International, 2009, vol. 41, # 2, p. 152 - 155
[3] Arkivoc, 2010, vol. 2010, # 2, p. 71 - 96
2
[ 4460-86-0 ]
[ 1530-32-1 ]
[ 5273-86-9 ]
[ 2883-98-9 ]
[ 80423-94-5 ]
Reference:
[1] Organic Preparations and Procedures International, 2007, vol. 39, # 5, p. 514 - 517
3
[ 74-96-4 ]
[ 603-35-0 ]
[ 1530-32-1 ]
Yield
Reaction Conditions
Operation in experiment
91.8%
for 10 h; Reflux
In a 1500 ml reaction flask, 54 g (0.5 mol) of ethyl bromide and210 g (0.8 mol) of triphenylphosphine and 1000 ml of toluene were added,Heated to reflux with stirring for 10 hours, the reaction was cooled to 50 ° C,A large amount of solid precipitated, suction filtered, the filter cake was washed with toluene (50ml * 3 times)The solid was dried in a vacuum oven at 50 ° C,Ethyl triphenylphosphonium bromide 170.4g, yield 91.8percent
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Reference Example 112 To dimethylsulfoxide (20 mL) was added sodium hydride (60% in oil, 0.6 g) at room temperature, the mixture was kept to 55C and stirred for 1 hour. Ethyl (triphenyl)phosphonium bromide (5.57 g) was added and the mixture was stirred at 55C for 45 minutes. The reaction solution was returned to room temperature, and tert-butyl (2R)-2-formylpyrrolidine-1-carboxylate (2 g) was dissolved in dimethyl sulfoxide (4 mL), added, and the mixture was stirred for 16 hours. Iced water was poured into the reactant, and extracted with ethyl acetate. The extracts were washed with water, dried and concentrated. The obtained residue was purified by silica gel column chromatography to obtain tert-butyl 2-[(1E)-prop-1-enyl]pyrrolidine-1-carboxylate (1.6 g). 1H-NMR (200 MHz, CDCl3) delta: 1.44(9H, s), 1.50-2.20(7H, m), 3.30-3.50(2H, m), 4.10-4.65(1H, m), 5.20-5.60(2H, m).
With lithium hexamethyldisilazane; In tetrahydrofuran; at -78 - 20℃;
Intermediate XLIII: (2R)-2-[(1Z)-prop-1-enyl]pyrrolidine; Step A: Wittig Reaction; To a solution of Boc-D-prolinal (0.5 g, 2.5 mmol) in tetrahydrofuran (10 mL) was added ethyltriphenylphosphonium bromide (3.7 g, 10.0 mmol) and cooled to-78 C. Then added dropwise lithium hexamethyldisilazide 1.0 M in THF (12 mL) and continued stirring from-78 C to rt overnight. Upon completion as determined by TLC (99: 1 methylene chloride to methanol with ninhydrin) the mixture was quenched with 20% ammonium chloride solution and extracted with ethyl acetate. The organic was washed with brine, dried over sodium sulfate anhydrous and concentrated in vacuo very carefully as the product is volatile. Crude product was purified on silica gel using a 99:1 mixture of methylene chloride to methanol as mobile phase with ninhydrin to develop. Pure fractions were combined and dried to yield tert-butyl-(2R)-2-[(1Z)-prop-1-enyl]pyrrolidine-1-carboxylate. LC-MS m/z (minus t-butyl + 1) = 156. ¹H NMR (CD30D, 400 Mhz) 5.47-5.41 ppm (m, 1H), 5.34-5.28 (m, 1H), 4.58-4.53 (m, 1H), 3.42-3.34 (m, 3H), 2.14-2.06 (m, 1H), 1.96-1.77 (m, 2H), 1.70-1.58 (m, 3H), 1.42 (s, 9H).