Methyl iodide → HCID 178499345, compound

HRID 2388267Notes

Reaction equation

HRID 2388267 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]#[C:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:8][C:9]=1[N:10]([C@H:20]1[CH2:25][CH2:24][C@H:23]([OH:26])[CH2:22][CH2:21]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].I[CH3:34].[H-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]#[C:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[CH:8][C:9]=1[N:10]([C@H:20]1[CH2:21][CH2:22][C@H:23]([O:26][CH3:34])[CH2:24][CH2:25]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178499344HCID 178499344, compound

Product 1

HCID 178499345HCID 178499345, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(3,3-dimethyl-but-1-ynyl)-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (0.200 g, 0.435 mmol) in dry DMF (2.0 mL) is added iodomethane (0.136 mL, 2.18 mmol), the mixture is cooled to 0° C., and NaH (60% suspension in oil, 35 mg, 0.87 mmol) is added in portions over 5 min. The mixture is stirred at 0° C. for 1 h 40 min, and it is quenched by addition of water and acidified with 2N HCl. The mixture is diluted with ethyl acetate and washed with brine. The organic layer is separated, dried over Na2SO4, concentrated under reduced pressure. The residue is purified by column chromatography on silica gel eluting with 0→50% ethyl acetate in hexane to give 5-(3,3-dimethyl-but-1-ynyl)-3-[(trans-4-methoxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (65 mg, 32%).

Workup

  1. customit is quenched by addition of water
  2. additionThe mixture is diluted with ethyl acetate
  3. washwashed with brine
  4. customThe organic layer is separated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by column chromatography on silica gel eluting with 0→50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-957dfecf460a446094d0d0e6c74a58fc
Source dataset
uspto-grants-2012_09
Patent number
US08269014B2

Reaction notes

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