Tri-o-tolylphosphine → methyl (R)-alpha-t-butoxycarbonylamino-7-chloro-3-diethylphosphonomethyl-6-methyl-2-quinolinepropionate

HRID 726649Notes

Reaction equation

HRID 726649 reaction equation
[CH3:1][O:2][C:3](=[O:15])[C@@H:4]([CH2:13]I)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Br[C:39]1[C:48]([CH2:49][P:50]([O:55][CH2:56][CH3:57])([O:52][CH2:53][CH3:54])=[O:51])=[CH:47][C:46]2[C:41](=[CH:42][C:43]([Cl:59])=[C:44]([CH3:58])[CH:45]=2)[N:40]=1>C1(C)C=CC=CC=1.CC(N(C)C)=O.C(OCC)(=O)C.[Cu].Cl[Pd]Cl>[C:9]([O:8][C:6]([NH:5][C@H:4]([CH2:13][C:39]1[C:48]([CH2:49][P:50]([O:52][CH2:53][CH3:54])([O:55][CH2:56][CH3:57])=[O:51])=[CH:47][C:46]2[C:41](=[CH:42][C:43]([Cl:59])=[C:44]([CH3:58])[CH:45]=2)[N:40]=1)[C:3]([O:2][CH3:1])=[O:15])=[O:7])([CH3:12])([CH3:11])[CH3:10]

Participants

9

Reactant 3

HCID 80271Tri-o-tolylphosphineHCID 11416215(S)-Methyl 2-Boc-amino-3-iodopropionateHCID 542836542-Bromo-7-chloro-3-diethylphosphonomethyl-6-methylquinoline

Product 1

HCID 54322860methyl (R)-alpha-t-butoxycarbonylamino-7-chloro-3-diethylphosphonomethyl-6-methyl-2-quinolinepropionateYield 75.3%

Reagents, catalysts & solvents 5

HCID 23978CopperCatalystHCID 24290Palladium ChlorideCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of N-t-butoxycarbonyl-3-iodo-D-alanine methyl ester (0.81 g, 2.46 mmol) in dry toluene (12 ml) and dry dimethylacetamide (0.8 ml) was added to a nitrogen purged flask charged with zink-copper couple (0.32 g, 4.92 mmol). The mixture was treated in an ultrasonic bath for 1 h until no starting material remained (as judged by TLC). A mixture of PdCl2 (23 mg, 0.13 mmol) and tri-o-tolylphosphine (79 mg, 0.26 mmol) was added followed by 2-bromo-7-chloro-3-diethylphosphonomethyl-6-methylquinoline (0.5 g, 1.23 mmol) and sonication was continued for 3 hours at 50°-60° C. After cooling the reaction mixture was diluted with ethyl acetate, extracted with saturated sodium hydrogen carbonate solution, dried over MgSO4 and evaporated. The crude product was subjected to chromatography on silica gel with ethyl acetate as eluant to yield 0.49 g of methyl (R)-α-t-butoxycarbonylamino-7-chloro-3-diethylphosphonomethyl-6-methyl-2-quinolinepropionate.

Workup

  1. additionThe mixture was treated in an ultrasonic bath for 1 h until no starting material
  2. additionwas added
  3. temperatureAfter cooling the reaction mixture
  4. extractionextracted with saturated sodium hydrogen carbonate solution
  5. dry with materialdried over MgSO4
  6. customevaporated

Sources & evidence

ORD record
ord-80387134cf0a4998ba7062ae44924014
Source dataset
uspto-grants-1998_01
Patent number
US05710139

Reaction notes

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