Trifluoroacetic acid → trans-Ethyl-1-benzyl-4-({[tertbutyl(dimethyl)silyl]oxy}methyl)pyrrolidine-3-carboxylate

HRID 577728Notes

Reaction equation

HRID 577728 reaction equation
[Si:1]([O:8][CH2:9]/[CH:10]=[CH:11]/[C:12]([O:14][CH2:15][CH3:16])=[O:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:17]([N:24]([CH2:28][Si](C)(C)C)[CH2:25]OC)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:15]([O:14][C:12]([C@H:11]1[C@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:28][N:24]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:25]1)=[O:13])[CH3:16]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 10490523(E)-4-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]-2-butenoic Acid Ethyl Ester

Product 1

HCID 89460104trans-Ethyl-1-benzyl-4-({[tertbutyl(dimethyl)silyl]oxy}methyl)pyrrolidine-3-carboxylateYield 51.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of ethyl (2E)-4-{[tert-butyl(dimethyl)silyl]oxy}but-2-enoate (3.27 g, 13.4 mmol) and N-benzyl-1-methoxy-N-((trimethylsilyl)methyl)methanamine (4.14 g, 17.5 mmol) in CH2Cl2 (30 mL) was added TFA (0.280 mL, 3.64 mmol) at 0° C. The reaction was stirred at rt overnight. The mixture was quenched with water (50 mL) and extracted with EtOAc (two×50 mL). The combined organic layers were dried over MgSO4 and concentrated. The residue was purified via flash chromatography eluting with 20% EtOAc/heptane to give the title compound as a pale yellow oil (2.61 g, 53 yield). 1H NMR (400 MHz, chloroform-d) δ ppm 7.08-7.41 (m, 5H), 4.10 (q, J=7.13 Hz, 2H), 3.42-3.73 (m, 4H), 2.37-2.90 (m, 6H), 1.22 (t, J=7.05 Hz, 3H), 0.84 (s, 9H), 0.00 (d, J=1.26 Hz, 6H).

Workup

  1. customThe mixture was quenched with water (50 mL)
  2. extractionextracted with EtOAc (two×50 mL)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. customThe residue was purified via flash chromatography
  6. washeluting with 20% EtOAc/heptane

Sources & evidence

ORD record
ord-13fa6251045140cd8f662e005c014300
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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