Acetic Acid → 2-(Benzhydryl-amino)-3-hydroxy-3-(6-methoxy-[1,5]naphthyridin-4-yl)-propionic acid methyl ester

HRID 1640512Notes

Reaction equation

HRID 1640512 reaction equation
[CH3:1][O:2][C:3]1[N:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[C:6]2[CH:13]=[O:14].[CH3:15][O:16][C:17](=[O:33])[CH2:18][N:19]=[C:20]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(NCC=C)C=C.CC(O)=O.[BH3-]C#N.[Na+]>C1(C)C=CC=CC=1.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.[Zn+2].CC(=O)OCC>[CH3:15][O:16][C:17](=[O:33])[CH:18]([NH:19][CH:20]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH:13]([OH:14])[C:6]1[C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[N:4]=2)[N:9]=[CH:8][CH:7]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 31279DiallylamineHCID 563248Methyl N-(diphenylmethylidene)glycinateHCID 5003444Sodium cyanoborohydrideHCID 665231381,5-Naphthyridine-4-carboxaldehyde, 6-methoxy-

Product 1

HCID 667364442-(Benzhydryl-amino)-3-hydroxy-3-(6-methoxy-[1,5]naphthyridin-4-yl)-propionic acid methyl esterYield 66.3%

Reagents, catalysts & solvents 3

HCID 104671Zinc trifluoromethanesulfonateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of Zn(OTf)2 (0.064 g, 0.17 mmol) and 6-methoxy-[1,5]naphthyridine-4-carbaldehyde (0.5 g, 2.6 mmol) and molecular sieves (4 Å, 0.66 g) in toluene (13 mL) at 0° C. was treated with (benzhydrylidene-amino)-acetic acid methyl ester (0.44 g, 1.7 mmol) and diallylamine (0.25 g, 1.7 mmol). The mixture was left at 4° C. over the weekend. The reaction was quenched by careful addition of Na2CO3 and filtered. The filtrate was diluted with EA and water and the 2 phases separated. The org. phase was dried over MgSO4 and concentrated. The residue was dissolved in MeOH (10 mL) and AcOH (0.175 g, 3 mmol) and NaCNBH3 (0.166 g, 2.6 mmol) was added. The mixture was stirred at rt overnight and partitioned between a NaHCO3 solution and EA. The org. phase was dried over MgSO4 and concentrated. Chromatography on SiO2 (Hex/EA 1:1) gave the title intermediate as a yellow oil (0.5 g, 64% yield).

Workup

  1. waitThe mixture was left at 4° C. over the weekend
  2. customThe reaction was quenched by careful addition of Na2CO3
  3. filtrationfiltered
  4. additionThe filtrate was diluted with EA and water
  5. customthe 2 phases separated
  6. dry with materialphase was dried over MgSO4
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in MeOH (10 mL)
  9. custompartitioned between a NaHCO3 solution and EA
  10. dry with materialphase was dried over MgSO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-bf1ef12fbb50441aafa2cb911c97943e
Source dataset
uspto-grants-2012_02
Patent number
US08114867B2

Reaction notes

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