4-Toluenesulfonyl chloride → HCID 69022230, compound

HRID 1864692Notes

Reaction equation

HRID 1864692 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](=[N:10]/[C:4]3[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[C:3]=3[CH3:29])/[O:12][CH2:27]2)[CH2:17][CH2:16]1)([C:22]([CH3:23])([CH3:25])[CH3:24])([CH3:20])[CH3:21].[Cl:1][C:2]1[C:3]([CH3:29])=[C:4]([N:10]2[CH2:26][C@@:14]3([CH3:27])[C@@H:15]([OH:18])[CH2:16][CH2:17][N:13]3[C:11]2=[O:12])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Participants

8

Reactant 3

HCID 73974-Toluenesulfonyl chloride2×HCID 23665647Potassium tert-butoxide3×HCID 70944587HCID 70944587, compound

Product 2

HCID 69022230HCID 69022230, compoundHCID 178430160HCID 178430160, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2S,3S)-3-(tert-butyldimethylsilanyloxy)-2-hydroxymethyl-2-methylpyrrolidine-1-carboxylic acid (3-chloro-4-cyano-2-methyl-phenyl)-amide (3D) (140 mg, 0.320 mmol) in THF (3 mL) at 0° C. was added a 1 M solution of potassium tert-butoxide in THF (1.12 mL, 1.12 mmol) followed by a solution of p-toluenesulfonyl chloride (152 mg, 0.800 mmol) in THF (1 mL). After 10 min, additional potassium tert-butoxide (200 μL) and p-toluenesulfonyl chloride (5 mg) were added. After another 10 min, additional potassium tert-butoxide (500 μL) was added and the reaction stirred for 2 h. 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 compound 3E (8.0 mg, LC/MS m/z 420 [M+H]+), and (7S,7aS)-2-chloro-4-(7-hydroxy-7a-methyl-3-oxo-hexahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile (54.0 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-d6d5ccf70f664f46b20749d1c8ca1947
Source dataset
uspto-grants-2009_12
Patent number
US07625923B2

Reaction notes

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