Chlorotrimethylsilane → racemic methyl (1S,2R)-2-methyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclohexanecarboxylate

HRID 736833Notes

Reaction equation

HRID 736833 reaction equation
[CH3:1][C:2]12[NH:9]C(=O)[CH:7]1[CH2:6][CH2:5][CH2:4][CH2:3]2.[CH3:11][Si](Cl)(C)C.Cl.[CH3:17][C:18]1[CH:27]=[C:26]([CH2:28][O:29][C:30]2[CH:35]=[CH:34][C:33]([S:36](Cl)(=[O:38])=[O:37])=[CH:32][CH:31]=2)[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:19]=1.[C:40](=[O:43])(O)[O-:41].[Na+]>CO.ClCCl.C(OCC)(=O)C>[CH3:1][C@@:2]1([NH:9][S:36]([C:33]2[CH:34]=[CH:35][C:30]([O:29][CH2:28][C:26]3[C:25]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[N:19]=[C:18]([CH3:17])[CH:27]=3)=[CH:31][CH:32]=2)(=[O:38])=[O:37])[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[C:40]([O:41][CH3:11])=[O:43]

Participants

8

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 516892Sodium BicarbonateHCID 775591136-Methyl-7-azabicyclo[4.2.0]octan-8-oneHCID 866078654-(2-Methylquinolin-4-ylmethoxy)benzenesulfonyl chloride hydrochloride

Product 1

HCID 90702325racemic methyl (1S,2R)-2-methyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclohexanecarboxylateYield 23%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of racemic (1S,6R)-6-methyl-7-azabicyclo[4.2.0]octan-8-one (0.46 g, 3.3 mmol) in methanol (9 mL) at 0° C. was added trimethylsilylchloride (0.84 g, 2 eq). The reaction was stirred at room temperature overnight, concentrated and chased with methanol/benzene to afford the crude amino ester. To a solution of the crude amino ester in dichloromethane (10 mL) was added 4-(2-methyl-quinolin-4-ylmethoxy) -benzenesulfonyl chloride hydrochloride (1.5 g, 1.2 eq) followed by saturated sodium bicarbonate and ethyl acetate (2 mL). The reaction was stirred overnight and the methylene chloride was removed in vacuo. The mixture was then extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered and concentrated. Chromatography on silica gel eluting with a gradient of 40-60% ethyl acetate/hexanes afforded racemic methyl (1S,2R)-2-methyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclohexanecarboxylate (0.375 g, 23% over two steps). MS: 483.1 (M+H)+

Workup

  1. concentrationconcentrated
  2. customto afford the crude amino ester
  3. stirringThe reaction was stirred overnight
  4. customthe methylene chloride was removed in vacuo
  5. extractionThe mixture was then extracted with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-15d37da885764bd6b1adcae048f53316
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Reaction notes

Loading…