p-Toluenesulfonic acid → (1S)-N-(cyclopropylmethyl)-1-(4-fluorophenyl)prop-2-en-1-amine

HRID 1392109Notes

Reaction equation

HRID 1392109 reaction equation
C(=O)(OC)O[CH2:3]/[CH:4]=[CH:5]/[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1.C1([C@@H]([N:24]([C@H:48]([C:50]2[CH:55]=[CH:54]C=CC=2)C)P2OC3C=CC4C=CC=CC=4C=3C3C4C(C=CC=3O2)=CC=CC=4)C)C=CC=CC=1.C1(NC)CC1.CC1C=CC(S(O)(=O)=O)=CC=1>C1COCC1.CCO>[CH:50]1([CH2:48][NH:24][C@H:5]([C:6]2[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=2)[CH:4]=[CH2:3])[CH2:55][CH2:54]1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 11029756N-MethylcyclopropanamineHCID 11731247N,N-Bis((S)-1-phenylethyl)dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin-4-amineHCID 16753254(2E)-3-(4-fluorophenyl)prop-2-en-1-yl methyl carbonate

Product 1

HCID 69211561(1S)-N-(cyclopropylmethyl)-1-(4-fluorophenyl)prop-2-en-1-amineYield 851.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (2E)-3-(4-fluorophenyl)prop-2-en-1-yl methyl carbonate (420 mg), N,N-bis[(1S)-1-phenylethyl]dinaphtho[1,2-f:2′,1′-d][1,3,2]dioxaphosphepin-4-amine (108 mg), [Ir(COD)Cl]2 (27 mg), cyclopropyl methyl amine (374 μL) and EtOH (5 mL) was stirred under refluxing EtOH for 6H under N2. The progress of the reaction was monitered by HPLC. At the end of the reaction, addition of co-solvent (20 ml EtOH and 20 ml THF) and MP-TsOH resin (6 g) and the mixture was allowed to stirred at RT with swilling every 15 mins for 2-3 hours. Filtered the resin and washed the resin with plenty of EtOH, THF, DCM. The resin was taken up in 3.5N NH3 in MeOH (20 mL) and let it stir for overnight. Filtered the resin and washed the resin excessively with EtOH, THF and DCM. Combined the filtrate and evaporated all the solvent. The crude product was purified by flash chromatography (10% EtOAc/Hexane) to afford the title compound as a viscous oil (350 mg, 88%). 1H NMR (300 MHz, CDCl3) revealed branched/linear ratio (9:1) 0.27 (m, 2H), 0.47 (m, 2H), 1.10 (m, 1H), 2.40 (m, 2H), 4.51(m, 1H), 5.25-5.39 (m, 3H), 7.02-7.22 (m, 4H). MS APCI, m/z=206 (M+1). LC/MS 0.85 min., Method A. 94% ee was determined by NMR in the presence of TFAE-d11

Workup

  1. stirringto stirred at RT
  2. filtrationFiltered the resin
  3. washwashed the resin with plenty of EtOH, THF, DCM
  4. stirringstir for overnight
  5. filtrationFiltered the resin
  6. washwashed the resin excessively with EtOH, THF and DCM
  7. customevaporated all the solvent
  8. customThe crude product was purified by flash chromatography (10% EtOAc/Hexane)

Sources & evidence

ORD record
ord-0577d84bb1e148388e33f16e32c3020a
Source dataset
uspto-grants-2008_03
Patent number
US07342007B2

Reaction notes

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