4-Methylmorpholine → HCID 18451929, compound

HRID 1271487Notes

Reaction equation

HRID 1271487 reaction equation
[OH-].[Na+].[CH:3]1([CH2:6][NH:7][CH2:8][CH:9]([NH:16][CH2:17][CH2:18][C:19]([O:21]CC)=O)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:5][CH2:4]1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.CN1CCOCC1>CO.CN(C)C=O>[CH:3]1([CH2:6][N:7]2[C:19](=[O:21])[CH2:18][CH2:17][NH:16][CH:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH2:8]2)[CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 14798Sodium HydroxideHCID 199401P,P-Diphenylphosphinic azideHCID 18451932HCID 18451932, compound

Product 1

HCID 18451929HCID 18451929, compoundYield 90.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Sodium hydroxide (1M; 6.53 mL, 6.53 mmol) was added to a solution of ethyl N-{2-[(cyclopropylmethyl)amino]-1-phenylethyl}-beta-alaninate (1.81 g, 6.22 mmol) in methanol (10 mL). After 1 h, the mixture was concentrated and azeotroped with toluene (3×) to give the crude acid. Diphenylphosphoryl azide (2.68 ml, 12.43 mmol) was added to a solution of the crude acid (1.77 g, 6.22 mmol) and 4-methylmorpholine (1.37 mL, 12.4 mmol) in N,N-dimethylformamide (124 mL). After 18 h, the reaction was concentrated and diluted with water. The mixture was extracted with dichloromethane (3×), and the combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. Purification by silica gel chromatography [100% dichloromethane→90% dichloromethane/10% (10% ammonium hydroxide/methanol)] gave the title compound (1.38 g). MS 245 (M+1). 1H NMR (500 MHz, CDCl3) δ 7.47–7.30 (m, 5H), 3.89–3.88 (m, 2H), 3.65 (dd, J=13.9, 6.6 Hz, 1H), 3.31–3.26 (m, 1H), 3.24–3.21 (m, 1H), 3.02–2.93 (m, 3H), 2.70–2.65 (m, 1H), 1.02–0.97 (m, 1H), 0.58–0.49 (m, 2H), 0.28–0.21 (m, 2H).

Workup

  1. concentrationthe mixture was concentrated
  2. customazeotroped with toluene (3×)
  3. customto give the crude acid
  4. waitAfter 18 h
  5. concentrationthe reaction was concentrated
  6. additiondiluted with water
  7. extractionThe mixture was extracted with dichloromethane (3×)
  8. dry with materialthe combined organic extracts were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by silica gel chromatography [100% dichloromethane→90% dichloromethane/10% (10% ammonium hydroxide/methanol)]

Sources & evidence

ORD record
ord-fcf18c4bf418421a80d692985a6c9c67
Source dataset
uspto-grants-2007_04
Patent number
US07205292B2

Reaction notes

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