Methyl iodide → HCID 18787150, compound

HRID 1107451Notes

Reaction equation

HRID 1107451 reaction equation
[C:1]([N:5]1[CH:9]2[CH:10]=[CH:11][CH:6]1[C:7]([C:21]1[CH:22]=[CH:23][C:24]([Cl:27])=[N:25][CH:26]=1)=[C:8]2[S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:14])=[O:13])([O:3][CH3:4])=[O:2].[C:28](N1C2CCC1C(C1C=CC(Cl)=NC=1)C2S(C1C=CC=CC=1)(=O)=O)(OC)=O.C([Li])CCC.CI>CO.O1CCCC1.O>[C:1]([N:5]1[CH:9]2[CH2:10][CH2:11][CH:6]1[CH:7]([C:21]1[CH:22]=[CH:23][C:24]([Cl:27])=[N:25][CH:26]=1)[C:8]2([CH3:28])[S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:14])=[O:13])([O:3][CH3:4])=[O:2]

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 23298261HCID 23298261, compoundHCID 23298267HCID 23298267, compoundHCID 178418339Butyllithium

Product 1

HCID 18787150HCID 18787150, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

7-Carbomethoxy-2-(2-chloro-5-pyridyl)-3-phenylsulfonyl-7-azabicyclo[2.2.1]hept-2,5-diene (23) is hydrogenated in methanol containing 10% Pd-C until both double bonds are saturated. The product, 7-carbomethoxy-2-(2-chloro-5-pyridyl)-3-phenylsulfonyl-7-aza-bicyclo[2.2.1]heptane 39, is dissolved in dry tetrahydrofuran and treated with n-butyl lithium (1.1 eq) at -30 to 0° C., followed by methyl iodide (1-1 eq) in tetrahydrofuran. The reaction mixture is then stirred at room temperature and poured into iced water. The product is extracted with ether and washed with water. After drying and evaporation of the ether solution, the crude product is chromatographed on a silica gel column, using a mixture of petroleum ether and ethyl acetate (3:1 by volume) to yield stereoisomers of 7-carbomethoxy-2-(2-chloro-5-pyridyl)-3-methyl-3-phenylsulfonyl-7-aza-bicyclo[2.2.1]heptane (40). The alkylation products are each treated with sodium amalgam as in Example 30 to remove the phenylsulfonyl group, followed by acid cleavage of the 7-carbomethoxy group as in Example 32 to yield isomeric 3-methyl analogs of compound 8 and 8'.

Workup

  1. extractionThe product is extracted with ether
  2. washwashed with water
  3. customAfter drying
  4. customevaporation of the ether solution
  5. customthe crude product is chromatographed on a silica gel column
  6. additiona mixture of petroleum ether and ethyl acetate (3:1 by volume)

Sources & evidence

ORD record
ord-001b4a4d348c463fbea50f322dec8ebc
Source dataset
uspto-grants-2000_05
Patent number
US06060473

Reaction notes

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