4-Methylmorpholine → (S)-N-((S)-6-Cyano-1,2,3,4-tetrahydroquinolin-3-yl)-2-hydroxy-2-phenylacetamide

HRID 1363081Notes

Reaction equation

HRID 1363081 reaction equation
Cl.Cl.[NH2:3][CH:4]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:14]#[N:15])[CH:11]=2)[NH:6][CH2:5]1.[C:16](O)(=[O:25])[C@H:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[OH:18].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[C:14]([C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[NH:6][CH2:5][C@@H:4]([NH:3][C:16](=[O:25])[C@@H:17]([OH:18])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:13]2)#[N:15]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 439616(S)-mandelic acidHCID 1317281063-Amino-1,2,3,4-tetrahydroquinoline-6-carbonitrile, dihydrochloride

Product 1

HCID 66757271(S)-N-((S)-6-Cyano-1,2,3,4-tetrahydroquinolin-3-yl)-2-hydroxy-2-phenylacetamideYield 20%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1D (10.03 g, 40.7 mmol) in DMF (100 mL) was added (S)-(+)-mandelic acid (7.45 g, 48.9 mmol), followed by EDAC (9.37 g, 48.9 mmol), HOBt (7.49 g, 48.9 mmol) and NMM (16.1 mL, 146.1 mmol). The reaction mixture was stirred at RT overnight, then diluted with EtOAc (200 mL), washed with water (50 mL×3), 1N aqueous HCl (50 mL), water (50 mL) and brine, dried (Na2SO4) and concentrated. The residue was chromatographed (silica gel) eluting with EtOAc/hexane (2:1), and the purified compound crystallized from acetone (3×) to give the title compound as the (S,S) diastereoisomer (2.54 g, 20% yield).

Workup

  1. washwashed with water (50 mL×3), 1N aqueous HCl (50 mL), water (50 mL) and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue was chromatographed (silica gel)
  5. washeluting with EtOAc/hexane (2:1)
  6. customthe purified compound crystallized from acetone (3×)

Sources & evidence

ORD record
ord-94e34bdf3e24411ba05451c497aab7dc
Source dataset
uspto-grants-2011_02
Patent number
US07884113B2

Reaction notes

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