4-Methylmorpholine → HCID 58635229, compound

HRID 350625Notes

Reaction equation

HRID 350625 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12](=[O:16])[C:13]([O-:15])=O)([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:18][O:19][C:20](=[O:24])[C@H:21]([CH3:23])[NH2:22].O.OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC.CN1CCOCC1.[K+].[Br-]>CN(C=O)C>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12]([C:13]([NH:22][C@@H:21]([CH3:23])[C:20]([O:19][CH3:18])=[O:24])=[O:15])=[O:16])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 253877Potassium BromideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733257Alanine methyl ester hydrochlorideHCID 22134611HCID 22134611, compoundHCID 178526939HCID 178526939, compound

Product 1

HCID 58635229HCID 58635229, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 3-L, 3-necked round-bottomed flask, equipped with a mechanic stirrer and a thermal probe (under nitrogen) was charged with the following solids: 2-(2-tert-Butylphenylamino)-2-oxoacetate (70.008 g, 316.402 mmol), alanine methyl ester hydrochloride (44.368 g, 317.862 mmol), hydroxybenzotriazole hydrate (HOBT) (47.324 g, 350.210 mmol), and 1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDAC.HCl) (121.668 g, 635.4 mmol). N,N′-dimethylformamide (DMF) (1250 mL) was added via graduated cylinder, and the reaction mixture stirred to partially dissolve and suspend the solid reagents. N-methylmorpholine (108 mL, 99.36 g, 982 mmol) was then added in one portion via graduated cylinder. After stirring at room temperature for 18 hours, the reaction mixture was partitioned between EtOAc (ca. 600 mL) and 1N HCl (ca. 500 mL). The aqueous phase was washed two times with EtOAc (ca. 300 mL), and the combined organic layers were washed successively with 1N HCl (ca. 300 mL), H2O (ca 300 mL), saturated NaHCO3 (ca. 300 mL), and brine (ca. 300 mL). The resulting pale yellow organic solution was dried over MgSO4, then concentrated to yield a pale yellow crystalline mass (95 g, 97%). TLC: (silica, 1:1 hexanes/EtOAc) Rf: 0.54. MP: 60.1–62.1° C.; IR (KBr) 3284, 1747, 1662, 1503, 1216, 755 cm−1; 1H NMR: (CDCl3, TMS) δ 9.55 (br, 1H), 8.01 (dd, J=7.8 Hz, J′=1.8 Hz, 1H), 7.42 (dd, J=7.8 Hz, J′=2.6 Hz, 1H), 7.15–7.31 (m, 2H), 4.64 (p, J=7.5 Hz, 1H), 3.80 (s, 3H), 1.54 (d, J=7.5 Hz, 3H), 1.46 (s, 9H) ppm.

Workup

  1. additiona thermal probe (under nitrogen) was charged with the following solids
  2. dissolutionto partially dissolve
  3. stirringAfter stirring at room temperature for 18 hours
  4. customthe reaction mixture was partitioned between EtOAc (ca. 600 mL) and 1N HCl (ca. 500 mL)
  5. washThe aqueous phase was washed two times with EtOAc (ca. 300 mL)
  6. washthe combined organic layers were washed successively with 1N HCl (ca. 300 mL), H2O (ca 300 mL), saturated NaHCO3 (ca. 300 mL), and brine (ca. 300 mL)
  7. dry with materialThe resulting pale yellow organic solution was dried over MgSO4
  8. concentrationconcentrated
  9. customto yield a pale yellow crystalline mass (95 g, 97%)

Sources & evidence

ORD record
ord-358c2919c0614bf8a841d5aac19a22b5
Source dataset
uspto-grants-2007_02
Patent number
US07183260B2

Reaction notes

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