Methyl iodide → methyl (1S,2R)-1-ethyl-2-[methyl({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxylate

HRID 736827Notes

Reaction equation

HRID 736827 reaction equation
[CH2:1]([C@:3]1([C:31]([O:33][CH3:34])=[O:32])[CH2:7][CH2:6][CH2:5][C@H:4]1[NH:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=[C:22]([CH3:30])[CH:21]=2)=[CH:14][CH:13]=1)(=[O:11])=[O:10])[CH3:2].[H-].[Na+].I[CH3:38]>C1COCC1>[CH2:1]([C@:3]1([C:31]([O:33][CH3:34])=[O:32])[CH2:7][CH2:6][CH2:5][C@H:4]1[N:8]([CH3:38])[S:9]([C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:23]=[C:22]([CH3:30])[CH:21]=2)=[CH:14][CH:13]=1)(=[O:10])=[O:11])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86607917HCID 86607917, compound

Product 1

HCID 86607918methyl (1S,2R)-1-ethyl-2-[methyl({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxylateYield 83%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 204 mg (0.423 mmol) of methyl (1S,2R)-1-ethyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxylate (Example 56, Step 3) in THF (1.5 mL) was added 60% sodium hydride (22 mg, 0.55 mmol) and the resulting mixture was stirred at room temperature for 1 h. Iodomethane (35 μL, 80 mg 0.56 mmol) was added and the reaction was stirred overnight and then quenched with saturated aqueous ammonium chloride. These steps were repeated twice more, until starting material was consumed, and the residue was purified by column chromatography on silica gel eluting with 50% ethyl acetate/hexanes to give methyl (1S,2R)-l -ethyl-2-[methyl({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclopentanecarboxylate (174 mg, 0.350 mmol, 83%) as a colorless solid. 1H NMR (400 MHz, CHLOROFORM-D) □ ppm 0.85 (t, J=7.33 Hz, 3H) 1.29-1.40 (m, 1H) 1.48-1.60 (m, 4H) 1.78-1.87 (m, 1H) 2.20-2.30 (m, J=7.01, 7.01, 7.01, 7.01 Hz, 2H) 2.57 (s, 3H) 2.75 (s, 3H) 3.71 (s, 3H) 5.55 (s, 2H) 7.11 (ddd, J=9.41, 2.78, 2.46 Hz, 2H) 7.42 (s, 1H) 7.55 (ddd, J=8.27, 6.88, 1.26 Hz, 1H) 7.70-7.76 (m, 3H) 7.90 (d, J=7.58 Hz, 1H) 8.09 (d, J=7.83 Hz, 1H).

Workup

  1. stirringthe reaction was stirred overnight
  2. customquenched with saturated aqueous ammonium chloride
  3. customwas consumed
  4. customthe residue was purified by column chromatography on silica gel eluting with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-5be19d3859c946b0811403d844677421
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Reaction notes

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