Hydrochloric Acid → 5-[(R)-2-{[2-(3-Aminophenyl)ethyl]benzylamino}-1-(tert-butyl-dimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-one

HRID 2412249Notes

Reaction equation

HRID 2412249 reaction equation
C([NH:20][C:21]1[CH:22]=[C:23]([CH2:27][CH2:28]OS(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)[CH:24]=[CH:25][CH:26]=1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH2:42]([NH:49][CH2:50][C@@H:51]([C:60]1[CH:69]=[CH:68][C:67]([O:70][CH2:71][C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)=[C:66]2[C:61]=1[CH:62]=[CH:63][C:64](=[O:78])[NH:65]2)[O:52][Si:53]([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(=O)(O)[O-].[Na+].Cl>C(#N)C.CCOC(C)=O.O>[NH2:20][C:21]1[CH:22]=[C:23]([CH2:27][CH2:28][N:49]([CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:50][C@@H:51]([C:60]2[CH:69]=[CH:68][C:67]([O:70][CH2:71][C:72]3[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=3)=[C:66]3[C:61]=2[CH:62]=[CH:63][C:64](=[O:78])[NH:65]3)[O:52][Si:53]([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54])[CH:24]=[CH:25][CH:26]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium Bicarbonate2×HCID 666727545-[(R)-2-benzylamino 1-(tert-butyldimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-oneHCID 866469604-Nitrobenzenesulfonic Acid 2-[3-(Tritylamino)phenyl]ethyl Ester

Product 1

HCID 667816275-[(R)-2-{[2-(3-Aminophenyl)ethyl]benzylamino}-1-(tert-butyl-dimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-oneYield 85.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred mixture of 4-nitrobenzenesulfonic acid 2-[3-(tritylamino)phenyl]ethyl ester (7.44 g, 13.2 mmol); 5-[(R)-2-benzylamino-1-(tert-butyldimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-one (5.42 g, 10.5 mmol) (see, e.g., U.S. Patent Publication No. 2006/0035931 A1, published Feb. 16, 2006) and sodium bicarbonate (3.32 g, 39.5 mmol) in acetonitrile (26.4 mL) was heated at 75° C. under nitrogen for 18 h. The mixture was cooled to room temperature and the pH was adjusted to pH <2 with aqueous hydrochloric acid (1 N, ˜40 mL). The mixture was stirred at room temperature for 1 h and then the pH of the mixture was adjusted to pH 7-8 with saturated aqueous sodium bicarbonate solution (˜30 mL). Water (˜50 mL) and EtOAc (˜50 mL) were added and the layers were separated (a small amount of dilute aqueous sodium chloride solution was added to improve separation). The aqueous layer was extracted with EtOAc (2×30 mL) and the combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (30-60% of EtOAc in hexanes) to give the title compound (5.7 g, 68% yield) as a light yellow foamy solid.

Workup

  1. customthe layers were separated (a small amount of dilute aqueous sodium chloride solution
  2. additionwas added
  3. customseparation)
  4. extractionThe aqueous layer was extracted with EtOAc (2×30 mL)
  5. dry with materialthe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel flash chromatography (30-60% of EtOAc in hexanes)

Sources & evidence

ORD record
ord-6fdc259f7103447ba9f774ff0ed71e5c
Source dataset
uspto-grants-2014_08
Patent number
US08816088B2

Reaction notes

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