Dichloromethane → 5-chloro-2-{[(2,2-difluoroethylidene)amino]-methyl}benzyl-1-[(9-hydroxy-9-H-fluoren-9-yl)carbonyl]-L-prolinamide

HRID 1058316Notes

Reaction equation

HRID 1058316 reaction equation
[OH:1][C:2]1([C:15]([N:17]2[CH2:34][CH2:33][CH2:32][C@H:18]2[C:19]([NH:21]CC2C=C(Cl)C=CC=2CN)=[O:20])=[O:16])[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.C(O[CH:38](O)[CH:39]([F:41])[F:40])C.[O-]S([O-])(=O)=O.[Mg+2].[CH2:49]([Cl:51])Cl>C1(C)C=CC=CC=1>[Cl:51][C:49]1[CH:9]=[CH:14][C:2]([CH2:15][N:17]=[CH:38][CH:39]([F:40])[F:41])=[C:3]([CH:4]=1)[CH2:8][C@@:18]1([C:19]([NH2:21])=[O:20])[CH2:32][CH2:33][CH2:34][N:17]1[C:15]([C:2]1([OH:1])[C:14]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:16]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 24083Sulfuric acid magnesium salt (1:1)HCID 27582461-Ethoxy-2,2-difluoroethanolHCID 9891135(S)-1-(9-Hydroxy-9H-fluorene-9-carbonyl)-pyrrolidine-2-carboxylic acid 2-aminomethyl-5-chloro-benzylamide

Product 1

HCID 865857755-chloro-2-{[(2,2-difluoroethylidene)amino]-methyl}benzyl-1-[(9-hydroxy-9-H-fluoren-9-yl)carbonyl]-L-prolinamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1-((9-hydroxy-9H-fluoren-9-yl)carbonyl)-N-(2-aminomethyl-5-chlorobenzyl)-L-prolinamide (65 mg, 0.14 mmol) in anhydrous toluene (1.0 mL) at 0° C. was added difluoroacetaldehyde ethylhemiacetal (20 mg, 0.16 mmol, 1.1 eq). The mixture was heated to 100° C. under nitrogen atmosphere for 40 min and was then treated with MgSO4. Heating was continued for another 2 h. The mixture was then cooled to room temperature and diluted with CH2Cl2. The solution was dried over MgSO4, filtered and concentrated to an orange oil which yielded N-(5-chloro-2-{[(2,2-difluoroethylidene)amino]-methyl}benzyl-1-[(9-hydroxy-9-H-fluoren-9-yl)carbonyl]-L-prolinamide as a foam on prolonged drying under high vacuum. (66 mg, 90%).

Workup

  1. temperatureHeating
  2. temperatureThe mixture was then cooled to room temperature
  3. dry with materialThe solution was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to an orange oil which

Sources & evidence

ORD record
ord-f0b8c7da2413463ab9622a3e947a7dac
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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