Water → HCID 20598048, compound

HRID 1839226Notes

Reaction equation

HRID 1839226 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([N:14]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:15](=[O:18])[CH2:16][CH3:17])[CH2:9]1)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+].O.BrC[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C(O)(C(F)(F)F)=O.C(Cl)Cl.C([O-])(O)=O.[Na+]>[CH2:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([N:14]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:15](=[O:18])[CH2:16][CH3:17])[CH2:9]1)[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7666Phenethyl bromideHCID 11430Potassium CarbonateHCID 54543759HCID 54543759, compound

Product 1

HCID 20598048HCID 20598048, compound

Reagents, catalysts & solvents 2

HCID 516892Sodium BicarbonateSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
70 °C

Procedure

3(R)-(Phenyl-propionyl-amino)-piperidine-1-carboxylic acid tert-butyl ester (169) (100 mg) was dissolved in a mixture of TFA-CH2Cl2 (1 ml, 20%) and stirred for 1 hr. After removal of solvent, the residue was dried under vacuum for 30 min and dissolved in 5 ml of CH2Cl2, washed with sat. K2CO3, dried (Na2SO4), filtered. After evaporation of the solvent, the residue was dissolved in CH3CN (1 ml). Then K2CO3 (125 mg, 3 eq), water (1 ml) and (2-bromoethyl)benzene (0.05 ml, 1.2 eq) was added. The mixture was heated at 70° C. for 12 hr. After cooling to room temperature, the mixture was diluted with sat. NaHCO3 (5 ml), extracted with CH2Cl2 (2×10 ml). The combined organic layers were dried (NaSO4), filtered and evaporated. The residue was purified by silica gel chromatography (100% CH2Cl2, 2%-4%MeOH in CH2Cl2) to give 170 as a colorless oil. 1H-NMR (300 MHz, CDCl3) δ 7.40 (m, 3H), 7.10 (m, 2H), 4.80 (m, 1H), 0.20 (m, 1H), 4.00 (m, 1H), 2.40 (m, 2H), 1.95 (m, 3H), 1.61 (m, 1H), 1.51 (m, 1H), 1.50 (s, 9H), 1.30 (m, 1H), 1.00 (t, 3H) ppm; LRMS (calculated for C22H28N2O2)+336, found 336; IR (film) 2978, 2937, 2860, 1693, 1662, 1698, 1494, 1422, 1363, 1264, 1151, 1386, 1182 cm−1.

Workup

  1. customAfter removal of solvent
  2. customthe residue was dried under vacuum for 30 min
  3. dissolutiondissolved in 5 ml of CH2Cl2
  4. washwashed with sat. K2CO3
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customAfter evaporation of the solvent
  8. dissolutionthe residue was dissolved in CH3CN (1 ml)
  9. temperatureAfter cooling to room temperature
  10. extractionextracted with CH2Cl2 (2×10 ml)
  11. dry with materialThe combined organic layers were dried (NaSO4)
  12. filtrationfiltered
  13. customevaporated
  14. customThe residue was purified by silica gel chromatography (100% CH2Cl2, 2%-4%MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-0348795f0f4243f79285ec1e3b74efa4
Source dataset
uspto-grants-2004_01
Patent number
US06677332B1

Reaction notes

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