Triethylamine → HCID 68511063, compound

HRID 1715118Notes

Reaction equation

HRID 1715118 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(CC)CC)C.[Br:35][CH2:36][C:37](Cl)=[O:38]>ClCCl>[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[NH:27][C:37](=[O:38])[CH2:36][Br:35])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 89602Bromoacetyl chlorideHCID 68509550HCID 68509550, compound

Product 1

HCID 68511063HCID 68511063, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-(4-allyloxycarbonyl-2-amino-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (25.0 g, 66.58 mmol, 1.0 equiv; example 1/step 4) in dichloromethane (250 mL) at 0° C. were slowly added triethylamine (16.84 g, 166.46 mol, 2.5 equiv) and bromoacetyl chloride (20.96 g, 133.17 mol, 2.0 equiv). After the addition was completed the cooling bath was removed and the reaction stirred for 2 h at rt. The reaction mixture was cooled again to 0° C., diluted with water and extracted with ethyl acetate. The combined organic fractions were washed with water, dried over Na2SO4, concentrated by evaporation under reduced pressure and purified with silica column chromatography eluting with hexane/ethyl acetate (65:35) to obtain 23.1 g (70%) of the title compound. 1H NMR (400 MHz, DMSO): δ 1.40 (s, 9H), 2.92 (br s, 2H), 3.62 (hr s, 1H), 4.03 (d, J=7.1, 2H), 4.30 (s, 2H), 4.72 (d, J=5.1, 2H), 5.24 (dd, J=10.5 Hz, J=1.0, 1H), 5.35 (dd, J=16.6 H, J=0.7, 1H), 5.50 (d, J=7.7 Hz, 1H), 5.98-6.05 (m, 1H), 6.82(d, J=8.8 Hz, 1H), 7.68 (dd, J=8.6 Hz, J=1.5 Hz, 1H), 7.73 (d, J=1.3 Hz, 1H), 9.43 (s, 1H).

Workup

  1. customat 0° C.
  2. additionAfter the addition
  3. customwas removed
  4. temperatureThe reaction mixture was cooled again to 0° C.
  5. additiondiluted with water
  6. extractionextracted with ethyl acetate
  7. washThe combined organic fractions were washed with water
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated by evaporation under reduced pressure
  10. custompurified with silica column chromatography
  11. washeluting with hexane/ethyl acetate (65:35)

Sources & evidence

ORD record
ord-5c5cf78323a94705a642c11d753357fe
Source dataset
uspto-grants-2010_09
Patent number
US07799806B2

Reaction notes

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