Morpholine → HCID 69019789, compound

HRID 1865730Notes

Reaction equation

HRID 1865730 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:22])[C@@H:9]([C:13]([CH3:21])([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[NH:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1>ClCCl.O>[CH3:22][N:8]([C@H:9]([C:10]([N:65]1[CH2:70][CH2:69][O:68][CH2:67][CH2:66]1)=[O:12])[C:13]([CH3:21])([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[CH3:14])[C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 10425339HCID 10425339, compound

Product 1

HCID 69019789HCID 69019789, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C., ice bath) solution of (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-methyl-3-phenylbutanoic acid (1.0 g, 3.30 mmol, WO 99/32509) and benzotriazole-1-yl-oxy-tris-pyrrolidinophosphonium hexafluorophosphate (1.46 g, 3.30 mmol) in anhydrous dichloromethane (5 ml) is added diisopropylethylamine (1.15 ml, 6.60 mmol) under an inert atmosphere. To this solution is added a solution of morpholine (0.313 ml, 3.60 mmol) in dichloromethane (2.5 ml). After stirring at 0° C. for 5-10 minutes, the cooling bath is removed, and the resulting reaction mixture is stirred at room temperature for 15-20 hours. The mixture is diluted with water, and the aqueous layer is extracted with ethyl acetate (3 times). The combined extracts are washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is chromatographed (silica gel, flash column), to give a dark yellow oil. (0.943 g, 76%) MS [M+H] 377.2

Workup

  1. customthe cooling bath is removed
  2. customthe resulting reaction mixture
  3. stirringis stirred at room temperature for 15-20 hours
  4. extractionthe aqueous layer is extracted with ethyl acetate (3 times)
  5. washThe combined extracts are washed with saturated sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is chromatographed (silica gel, flash column)
  10. customto give a dark yellow oil

Sources & evidence

ORD record
ord-31a4644ce09c4b07b4b5dddf458bc745
Source dataset
uspto-grants-2009_12
Patent number
US07626023B2

Reaction notes

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