Diisopropylethylamine → HCID 68506606, compound

HRID 1715116Notes

Reaction equation

HRID 1715116 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([O:23][CH2:24][CH:25]=[CH2:26])=[O:22])=[CH:17][C:16]=2[NH2:27])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)C(C)C)C.Cl[C:38](Cl)([O:40]C(=O)OC(Cl)(Cl)Cl)Cl>C1(C)C=CC=CC=1>[CH2:24]([O:23][C:21]([C:18]1[CH:19]=[CH:20][C:15]2[N:14]([CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]3)[C:38](=[O:40])[NH:27][C:16]=2[CH:17]=1)=[O:22])[CH:25]=[CH2:26]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 68509550HCID 68509550, compound

Product 1

HCID 68506606HCID 68506606, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
70 °C

Procedure

To a stirred solution of 4-(4-allyloxycarbonyl-2-amino-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (20.0 g, 53.27 mmol, 1.0 equiv; example 1/step 4) in toluene (200 mL) and N-ethyldiisopropylamine (17.21 g, 133.17 mol, 2.5 equiv) was added a solution of triphosgene (18.97 g, 63.92 mmol, 1.2 equiv) in toluene (200 mL) and the reaction mixture stirred at 70° C. for 1.5 h. The solvent was evaporated, the residue diluted with water and extracted with ethyl acetate. The combined organic fractions were washed with water and a sat. solution of NaCl, dried over Na2SO4 and concentrated by evaporation under reduced pressure. The crude material was further washed with a mixture of hexane/ethyl acetate (95:5) to yield 15.5 g (73%) of the title product as wvhite solid. 1H NMR (400 MHz, DMSO): δ 1.43 (s, 9H), 1.72 (d, J=10.8, 2H), 2.17-2.23 (m, 2H), 2.88 (br s, 2H), 4.09 (d, J=8.6 Hz, 2H), 4.38 (t, J=12.2 Hz, 1H), 4.77 (d, J=5.3 Hz, 2H), 5.26 (d, J=10.4 Hz, 1H), 5.40 (dd, J=17.2 Hz, J=1.4 Hz, 1H), 5.99-6.09 (m, 1H), 7.35 (d, J=8.4 Hz, 1H), 7.53 (d, J=1.3 Hz, 1H), 7.69-7.71 (m, 1H), 11.17 (s, 1H). 13C-NMR (100 MHz, DMSO): δ 28.04, 28.43, 50.32, 64.78, 78.79, 108.13, 109.18, 117.70, 121.69, 121.71, 122.67, 128.20, 132.81, 133.39, 153.78, 153.82, 165.36. MS (ISP): 402.2 [M+H]+.

Workup

  1. customThe solvent was evaporated
  2. additionthe residue diluted with water
  3. extractionextracted with ethyl acetate
  4. washThe combined organic fractions were washed with water
  5. dry with materiala sat. solution of NaCl, dried over Na2SO4
  6. concentrationconcentrated by evaporation under reduced pressure
  7. washThe crude material was further washed with a mixture of hexane/ethyl acetate (95:5)

Sources & evidence

ORD record
ord-86b20de2855746d2b3e68d085cecf856
Source dataset
uspto-grants-2010_09
Patent number
US07799806B2

Reaction notes

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