Potassium Carbonate → HCID 51356141, compound

HRID 1874633Notes

Reaction equation

HRID 1874633 reaction equation
[NH2:1][CH2:2][C@H:3]([NH:17][C:18](=[O:27])[C@H:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:20])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH:12]([CH3:16])[CH2:13][CH2:14][CH3:15])=[CH:6][CH:5]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:35][CH2:36][O:37][CH2:38][CH2:39]Br>C(#N)C>[CH3:16][CH:12]([CH2:13][CH2:14][CH3:15])[CH2:11][O:10][C:7]1[CH:6]=[CH:5][C:4]([C@@H:3]([NH:17][C:18](=[O:27])[C@H:19]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH3:20])[CH2:2][N:1]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 21521Bis(2-bromoethyl) etherHCID 58466401HCID 58466401, compound

Product 1

HCID 51356141HCID 51356141, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of (2S)-N-((1R)-2-amino-1-(4-(2-methylpentyloxy)phenyl)ethyl)-2-phenylpropanamide (100 mg, 0.271 mmol), prepared according to the procedure described in example 5, and potassium carbonate (75 mg, 0.543 mmol) in acetonitrile (4 mL) was added 2-bromoethyl ether (0.038 mL, 0.271 mmol). The reaction mixture was then heated at reflux for 18 h. The mixture was cooled to room temperature, filtered and the filtrate was concentrated. The residue was then transferred to a separatory funnel containing water (20 mL) and the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with brine (10 mL), dried over MgSO4, filtered and concentrated. The residue was purified by HPLC (acetonitrile/water with 0.1% TFA) to afford (2S)-N-((1R)-1-(4-(2-methylpentyloxy)phenyl)-2-morpholinoethyl)-2-phenylpropanamide.TFA (55 mg, 37% yield) as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.25-7.39 (m, 5H), 6.97 (d, J=8.6 Hz, 2H), 6.76 (d, J=8.8 Hz, 2H), 6.36 (br. s., 1H), 4.83 (d, J=5.0 Hz, 1H), 3.74 (dd, J=8.8, 5.8 Hz, 1H), 3.61-3.69 (m, 2H), 3.49-3.61 (m, 4H), 2.34-2.56 (m, 4H), 2.23-2.30 (m, 2H), 1.83-1.95 (m, 1H), 1.52 (d, J=7.3 Hz, 3H), 1.26-1.50 (m, 3H), 1.12-1.22 (m, 1H), 0.97 (d, J=6.8 Hz, 3H), 0.90 (t, J=7.3 Hz, 3H); LRMS (ESI) m/e 439.3 [(M+H)+, calcd for C27H39N2O3 439.3].

Workup

  1. customprepared
  2. temperatureThe reaction mixture was then heated
  3. temperatureat reflux for 18 h
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated
  6. customThe residue was then transferred to a separatory funnel
  7. additioncontaining water (20 mL)
  8. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL)
  9. washThe combined organic layers were washed with brine (10 mL)
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by HPLC (acetonitrile/water with 0.1% TFA)

Sources & evidence

ORD record
ord-181b086ec9454ea9a8a130bbbcbeefb7
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

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