Triethylamine → 1-(4-Nitrophenyl)-D-proline

HRID 1441373Notes

Reaction equation

HRID 1441373 reaction equation
[NH:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=[O:4].I[C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=1.C(N(CC)CC)C.C(=O)([O-])[O-].[K+].[K+]>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.CN(C=O)C.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu](I)I.O>[N+:16]([C:13]1[CH:14]=[CH:15][C:10]([N:1]2[CH2:8][CH2:7][CH2:6][C@@H:2]2[C:3]([OH:5])=[O:4])=[CH:11][CH:12]=1)([O-:18])=[O:17]

Participants

11

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 124951-Iodo-4-nitrobenzeneHCID 145742L-Proline

Product 1

HCID 262019311-(4-Nitrophenyl)-D-proline

Reagents, catalysts & solvents 6

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

Proline (3.5 g, 30.4 mmol), 4-iodonitrobenzene (7.2 g, 28.9 mmol), Pd(PPh3)4 (1.7 g, 5 mol %), copper iodide (0.3 g, 5 mol %), benzyltriethylammonium chloride (11.9 g, 52 mmol), triethylamine (8.3 ml, 60 mmol) and potassium carbonate (4.2 g, 30 mmol) were pre-mixed in DMF (60 ml)/water (6 ml). The reaction was heated at 80° C. for 8 hours. The DMF was removed in vacuo and the remaining black gum was dissolved in DCM, acidified with 2.0 N HCl (50 ml), extracted with DCM (3×100 ml), dried and solvent removed in vacuo to yield a black tar. The tar was dissolved in a minimum amount of DCM (7 ml) and loaded onto a 50 g silica column, the system was eluted with 20% EtOAc/isohexane, then 60% EtOAc/iso-hexane and finally 100% EtOAc. The title compound was obtained as an orange gum. NMR (299.954 MHz, CDCl3) 8.13 (d, 2H), 6.52 (d, 2H), 4.41 (d, 1H), 3.66 (t, 1H), 3.49 (q, 1H), 2.47-2.29 (m, 2H), 2.25-2.12 (m, 2H); m/z 237.

Workup

  1. customThe DMF was removed in vacuo
  2. dissolutionthe remaining black gum was dissolved in DCM
  3. extractionextracted with DCM (3×100 ml)
  4. customdried
  5. customsolvent removed in vacuo
  6. customto yield a black tar
  7. washthe system was eluted with 20% EtOAc/isohexane

Sources & evidence

ORD record
ord-24b3d78a3c134307a579fdd93af59cfe
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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