Triethylamine → (3-{(S)-2-[(R)-2-(8-Benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethylamino]propyl}phenyl)acetic Acid Methyl Ester

HRID 2412256Notes

Reaction equation

HRID 2412256 reaction equation
[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][C@@H:12]([NH2:14])[CH3:13])[CH:6]=1.C(N(CC)CC)C.CN1CCCC1=O.C(N[CH2:38][C@@H:39]([C:48]1[CH:57]=[CH:56][C:55]([O:58][CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)=[C:54]2[C:49]=1[CH:50]=[CH:51][C:52](=[O:66])[NH:53]2)[O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])C1C=CC=CC=1>CCOC(C)=O>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][C@@H:12]([NH:14][CH2:38][C@@H:39]([C:48]2[CH:57]=[CH:56][C:55]([O:58][CH2:59][C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=3)=[C:54]3[C:49]=2[CH:50]=[CH:51][C:52](=[O:66])[NH:53]3)[O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[CH3:13])[CH:6]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 13387N-methyl-2-pyrrolidoneHCID 666727545-[(R)-2-benzylamino 1-(tert-butyldimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-oneHCID 66782403Methyl [3-((S)-2-Aminopropyl)phenyl]acetate

Product 1

HCID 66773664(3-{(S)-2-[(R)-2-(8-Benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethylamino]propyl}phenyl)acetic Acid Methyl EsterYield 21.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of [3-((S)-2-aminopropyl)phenyl]acetic acid methyl ester (632 mg, 3.05 mmol) and triethylamine (1.27 mL, 9.15 mmol) in N-methylpyrrolidinone (3.4 mL, 35 mmol) was added to 8-benzyloxy-5-[(R)-2-bromo-1-(tert-butyldimethylsilanyloxy)-ethyl]-1H-quinolin-2-one (1.5 g, 3.0 mmol) (see, e.g., U.S. Patent Publication No. 2006/0035931 A1, published Feb. 16, 2006). The resulting mixture was microwaved (300 watts) at 100° C. for 1.5 h. The mixture was then diluted with EtOAc (20 mL) and this solution was washed repeatedly with brine (100 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-10% MeOH in DCM) to give the title compound (400 mg, 20% yield) as a yellow oil.

Workup

  1. customThe resulting mixture was microwaved (300 watts) at 100° C. for 1.5 h
  2. washthis solution was washed repeatedly with brine (100 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel flash chromatography (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-8578ca6758bc4cd3b5e9171985955344
Source dataset
uspto-grants-2014_08
Patent number
US08816088B2

Reaction notes

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