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

HRID 1162510Notes

Reaction equation

HRID 1162510 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 9D (325 mg, 0.94 mmol) in nitrogen degassed toluene:DMSO (2:1, 7 mL) at rt was added 9E (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 minutes, sealed and heated at 110° C. for 48 h. Cool to rt and extract with ethylacetate (50 mL) and wash with water followed by sat. aqueous NaHCO3. Dry over MgSO4, filter and concentrate. Purification by flash chromatography (40 g ISCO silica gel cartridge, 0-10% ethylacetate 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 minutes
  3. customsealed
  4. temperatureCool to rt
  5. extractionextract with ethylacetate (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% ethylacetate in hexane gradient)

Sources & evidence

ORD record
ord-cfbae85c939747b588b2f0b532e70ead
Source dataset
uspto-grants-2010_10
Patent number
US07820702B2

Reaction notes

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