Cesium carbonate → (2R,3S)-1-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-1-(3-chloro-4-cyano-2-methyl-phenylamino)ethyl]pyrrolidine

HRID 501618Notes

Reaction equation

HRID 501618 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C@@H:21]([NH2:23])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:24][C:25]1[C:32]([CH3:33])=[C:31](I)[CH:30]=[CH:29][C:26]=1[C:27]#[N:28].C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[C@@H:21]([NH:23][C:31]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25]([Cl:24])[C:32]=1[CH3:33])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 167319952-Chloro-4-iodo-3-methylbenzonitrileHCID 16732284(2R,3S)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-((1S)-1-aminoethyl) pyrrolidine

Product 1

HCID 16732285(2R,3S)-1-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-[(1S)-1-(3-chloro-4-cyano-2-methyl-phenylamino)ethyl]pyrrolidineYield 99%

Reagents, catalysts & solvents 1

HCID 22340214Dimethylsulfoxide tolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 61F (325 mg, 0.94 mmol) in degassed toluene:DMSO (2:1, 7 mL) at rt was added 61G (260 mg, 0.94 mmol), Cs2CO3 (614 mg, 1.89 mmol) and a solution of Pd2(dba)3 and (S)—N,N-dimethyl-1-[(R)-2-(diphenyphosphino)ferrocenyl]ethylamine (1:6 ratio, 0.06 mol %) in nitrogen degassed toluene (3 mL). The reaction was degassed with nitrogen for 30 min, sealed and heated at 110° C. for 48 h. Cool to rt and extract with EtOAc (50 mL) and wash with water followed by sat'd aqueous NaHCO3. Dry over MgSO4, filter and concentrate. Purification by flash chromatography (40 g ISCO silica gel cartridge, 0-10% EtOAc in hexane gradient) gave the title compound (460 mg): MS (ES) m/z 494.29 [M+H]+

Workup

  1. customa solution of Pd2(dba)3 and (S)—N,N-dimethyl-1-[(R)-2-(diphenyphosphino)ferrocenyl]ethylamine (1:6 ratio, 0.06 mol %) in nitrogen degassed toluene (3 mL)
  2. customThe reaction was degassed with nitrogen for 30 min
  3. customsealed
  4. temperatureCool to rt
  5. extractionextract with EtOAc (50 mL)
  6. washwash with water
  7. dry with materialDry over MgSO4
  8. filtrationfilter
  9. concentrationconcentrate
  10. customPurification by flash chromatography (40 g ISCO silica gel cartridge, 0-10% EtOAc in hexane gradient)

Sources & evidence

ORD record
ord-ee1eb99e0caa4147b36fff2a75fb3127
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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