Methyl iodide → HCID 15228773, compound

HRID 1741777Notes

Reaction equation

HRID 1741777 reaction equation
[Cl:1][C:2]1[CH:42]=[CH:41][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16][CH2:17][C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)=[CH:13][CH:14]=3)[C:9]([S:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[C:8]2[CH2:33][C:34]([CH3:40])([CH3:39])[C:35]([O:37][CH3:38])=[O:36])=[CH:4][CH:3]=1.[CH3:43][Si](C)(C)N[Si](C)(C)C.[K].IC.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1.C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16][CH:17]([C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)[CH3:43])=[CH:13][CH:14]=3)[C:9]([S:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[C:8]2[CH2:33][C:34]([CH3:40])([CH3:39])[C:35]([O:37][CH3:38])=[O:36])=[CH:41][CH:42]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 15225389Methyl 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-(quinolin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropanoateHCID 45051783Silanamine, 1,1,1-trimethyl-N-(trimethylsilyl)-, potassium salt

Product 1

HCID 15228773HCID 15228773, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of methyl 3-[N-(p-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl methoxy) indol-2-yl]-2,2-dimethylpropanoate (420 mg) (EP 419,049, Ex. 1, Step D) in THF (10 mL) at -78° C. was added 0.6M potassium hexamethyldisilazane in toluene (1.75 mL) and stirred at -78° C. for 5 min. Then iodomethane (87 ml) was added followed 15 min later by more 0.6M KHMDS in toluene (1.75 mL). The mixture was finally stirred at -78° C. for 30 min. The reaction mixture was poured into 25% NH4OAc (100 mL), extracted with ethyl acetate (2×100 mL), washed with brine (100 mL), and dried (MgSO4). The filtrate was evaporated to dryness and the residue was chromatographed on flash silica gel using ethyl acetate:hexane (15:85) as eluant to give the title product as a foam.

Workup

  1. stirringThe mixture was finally stirred at -78° C. for 30 min
  2. extractionextracted with ethyl acetate (2×100 mL)
  3. washwashed with brine (100 mL)
  4. dry with materialdried (MgSO4)
  5. customThe filtrate was evaporated to dryness
  6. customthe residue was chromatographed on flash silica gel

Sources & evidence

ORD record
ord-7c2a51d79fc04b6fb86cf25b0fdb54ee
Source dataset
uspto-grants-1994_08
Patent number
US05334719

Reaction notes

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