Lithium amide → (3S,alphaR)-t-Butyl 3-(N-allyl-alpha-methylbenzylamino)-4-pentenoate

HRID 1637038Notes

Reaction equation

HRID 1637038 reaction equation
[CH2:1]([NH:4][C@H:5]([CH3:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH:2]=[CH2:3].C([Li])CCC.[NH2-].[Li+].[C:20]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])(=[O:25])[CH:21]=[CH:22][CH:23]=[CH2:24]>O1CCCC1>[CH2:1]([N:4]([C@H:5]([CH3:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C@H:22]([CH:23]=[CH2:24])[CH2:21][C:20]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 24532Lithium amideHCID 2733823(R)-(+)-N-allyl-alpha-methylbenzylamineHCID 53950126t-Butyl pentadienoateHCID 178418339Butyllithium

Product 1

HCID 11109854(3S,alphaR)-t-Butyl 3-(N-allyl-alpha-methylbenzylamino)-4-pentenoateYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (R)-N-allyl-α-methylbenzylamine (24) (1.78 g, 11.1 mmol) in anhydrous tetrahydrofuran (20 ml) was cooled to -78° C. and 1.6M butyllithium (6.00 ml, 9.5 mmol) was added dropwise via a syringe. The resulting orange lithium amide solution was stirred at -78° C. for 1 hour. A solution of t-butyl pentadienoate (25) (1.137 g, 7.4 mmol) in anhydrous tetrahydrofuran (15 ml) was then added via a cannula and the solution was stirred for a further 1 hour. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution and the solution was allowed to warm to room temperature. Ethyl acetate (50 ml) was added, followed by brine (10 ml). The organic layer was separated, dried (magnesium sulphate) and filtered and the solvent evaporated under reduced pressure to afford a pale yellow oil. This was purified by flash chromatography on silica gel [ethyl acetate/petroleum ether (1:49)] to afford the title compound (Rf 0.25) as a colourless oil (1.97 g, 85%). δH (300 MHz; CDCl3) 7.40-7.19 (5H, m, Ph), 5.94-5.74 (2H, m, CH2 =CHCH and NCH2CH=CH2), 5.16-5.00 (4H, m, CH2 =CHCH and NCH2CH=CH2), 4.02 (1H, q, J=6.8, PhCHCH3), 3.90 (1H, app. q, J=7.1, NCHCH2), 3.15 (2H, d, J=6.1, NCH2CH=CH2), 2.41 (1H, dd, J=6.4 and 14.5, CH2CO2), 2.31 (1H, dd, J=14.5 and 8.3, CH2CO2), 1.42 (9H, s, (CH3)3C), 1.39 (3H, d, J=6.8, PhCHCH3).

Workup

  1. customThe reaction was quenched by the addition of saturated aqueous ammonium chloride solution
  2. additionEthyl acetate (50 ml) was added
  3. customThe organic layer was separated
  4. dry with materialdried (magnesium sulphate)
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customto afford a pale yellow oil
  8. customThis was purified by flash chromatography on silica gel [ethyl acetate/petroleum ether (1:49)]

Sources & evidence

ORD record
ord-b5b2668e8c934eaa970d010875a888ec
Source dataset
uspto-grants-2000_03
Patent number
US06037498

Reaction notes

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