4-Toluenesulfonyl chloride → (7R,7aR)-4-[7-(tert-Butyldimethylsilanyloxy)-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methyl-benzonitrile

HRID 751123Notes

Reaction equation

HRID 751123 reaction equation
[Cl:1][C:2]1[C:3]([CH3:29])=[C:4]([NH:10][C:11]([N:13]2[CH2:17][CH2:16][C@@H:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[C@:14]2([CH2:27]O)[CH3:26])=[O:12])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].CC(C)([O-])C.[K+].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C1COCC1.O.CCOC(C)=O>[Si:19]([O:18][C@H:15]1[C@:14]2([CH3:26])[N:13]([C:11](=[O:12])[N:10]([C:4]3[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[C:3]=3[CH3:29])[CH2:27]2)[CH2:17][CH2:16]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:20])[CH3:21]

Participants

7

Reactant 3

HCID 73974-Toluenesulfonyl chloride2×HCID 23665647Potassium tert-butoxide2×HCID 59754220(2R,3R)-3-(tert-Butyldimethylsilanyloxy)-2-hydroxymethyl-2-methylpyrrolidine-1-carboxylic acid (3-chloro-4-cyano-2-methyl-phenyl)-amide

Product 1

HCID 59754267(7R,7aR)-4-[7-(tert-Butyldimethylsilanyloxy)-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl]-2-chloro-3-methyl-benzonitrileYield 40.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2R,3R)-3-(tert-Butyldimethylsilanyloxy)-2-hydroxymethyl-2-methylpyrrolidine-1-carboxylic acid (3-chloro-4-cyano-2-methyl-phenyl)-amide (58D) (43 mg, 0.10 mmol) in THF (1 mL) at 0° C. was added a 1 M solution of potassium tert-butoxide in THF (0.24 mL, 0.24 mmol) followed by a solution of p-toluenesulfonyl chloride (22 mg, 0.12 mmol) in THF (0.5 mL). After 10 min, additional potassium tert-butoxide (50 □L) and p-toluenesulfonyl chloride (3 mg) were added. After another 10 min, the reaction was diluted with water and EtOAc and the layers were separated. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated and purified via preparative HPLC (Luna C-18, 100×21.2 mm, eluting with 60-100% solvent B (A=90% H2O—10% MeOH—0.1% TFA and B=10% H2O—90% MeOH—0.1% TFA) over 12 min; Flow rate at 20 mL/min; UV detection at 220 nm) to provide the title compound (17 mg). LC/MS m/z 420 [M+H]+.

Workup

  1. waitAfter another 10 min
  2. customthe layers were separated
  3. washThe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified via preparative HPLC (Luna C-18, 100×21.2 mm
  8. washeluting with 60-100% solvent B (A=90% H2O—10% MeOH—0.1% TFA and B=10% H2O—90% MeOH—0.1% TFA) over 12 min

Sources & evidence

ORD record
ord-fb89842c7eac4e5b9b1433a1046a7362
Source dataset
uspto-grants-2008_07
Patent number
US07405234B2

Reaction notes

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