4-Toluenesulfonyl chloride → HCID 86627648, compound

HRID 1907934Notes

Reaction equation

HRID 1907934 reaction equation
ClC1C=C(C=CC=1)C(OO)=O.[C:12]([O:16][C:17](=[O:37])[NH:18][CH2:19][CH2:20][CH2:21][N:22]1[C:34]2[C:33]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[N:27]=[CH:26][C:25]=2[N:24]=[C:23]1[CH2:35][Cl:36])([CH3:15])([CH3:14])[CH3:13].[OH-].[NH4+:39].C1(C)C=CC(S(Cl)(=O)=O)=CC=1>C(Cl)(Cl)Cl.ClCCl>[C:12]([O:16][C:17](=[O:37])[NH:18][CH2:19][CH2:20][CH2:21][N:22]1[C:34]2[C:33]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[N:27]=[C:26]([NH2:39])[C:25]=2[N:24]=[C:23]1[CH2:35][Cl:36])([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chloride2×HCID 14923Ammonium HydroxideHCID 70297m-Chloroperbenzoic acidHCID 66958458HCID 66958458, compound

Product 1

HCID 86627648HCID 86627648, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

3-Chloroperoxybenzoic acid (13.3 g of 77% max, 59.4 eq.) was added in portions over a period of 5 minutes to a solution of tert-butyl[3-(2-chloromethyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]carbamate (8.9 g, 23.7 mmol) in chloroform (200 mL). The reaction mixture was allowed to stir at ambient temperature overnight. Ammonium hydroxide (50 mL) was added and the reaction mixture was stirred vigorously. Para-toluensulfonyl chloride (5.43 g, 28.5 mmol) was added over a period of 5 minutes. The reaction mixture was stirred at ambient temperature for 2 hours; an additional 1 g of para-toluensulfonyl chloride was added and the reaction mixture was stirred for another hour. The reaction mixture was filtered to remove solids. The filtrate was transferred to a separatory funnel and the layers were separated. The organic layer was washed with 1:1 water:saturated aqueous sodium bicarbonate (2×150 mL). The combined aqueous was extracted with dichloromethane (2×150 mL) and ethyl acetate (1×100 mL). The combined organic extracts were concentrated under reduced pressure to provide 13.6 g of crude product as a brown foam. The foam was dissolved in dichloromethane (20 mL). The solution was divided and loaded onto two FLASH 40+M silica cartridges (90 g). The first cartridge was eluted sequentially with 1 L 1:1 ethyl acetate:hexanes, 5% methanol in 1:1 ethyl acetate:hexanes, and 10% methanol in 1:1 ethyl acetate:hexanes. The second cartridge was eluted sequentially with 1 L 1:1 ethyl acetate:hexanes, 7% methanol in 1:1 ethyl acetate:hexanes, and 7% methanol in 1:1 ethyl acetate:hexanes. The fractions containing product were combined and then concentrated under reduced pressure to provide 4.3 g of tert-butyl[3-(4-amino-2-chloromethyl-1H-imidazo[4,5-c]quinolin-1-yl)propyl]carbamate as a light yellow foam.

Workup

  1. stirringthe reaction mixture was stirred vigorously
  2. stirringThe reaction mixture was stirred at ambient temperature for 2 hours
  3. stirringthe reaction mixture was stirred for another hour
  4. filtrationThe reaction mixture was filtered
  5. customto remove solids
  6. customThe filtrate was transferred to a separatory funnel
  7. customthe layers were separated
  8. washThe organic layer was washed with 1:1 water
  9. extractionThe combined aqueous was extracted with dichloromethane (2×150 mL) and ethyl acetate (1×100 mL)
  10. concentrationThe combined organic extracts were concentrated under reduced pressure
  11. customto provide 13.6 g of crude product as a brown foam
  12. washThe first cartridge was eluted sequentially with 1 L 1:1 ethyl acetate
  13. washThe second cartridge was eluted sequentially with 1 L 1:1 ethyl acetate
  14. additionThe fractions containing product
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fe083731f287496b8bf6e2e0163f8b3c
Source dataset
uspto-grants-2013_12
Patent number
US08598192B2

Reaction notes

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