Sodium Chloride → HCID 68325408, compound

HRID 2403281Notes

Reaction equation

HRID 2403281 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:31].[Na+].[Cl-]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C:14]2[CH:19]=[CH:18][C:17]([N:20]([C:21]3[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=3)[CH3:31])=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 68325428HCID 68325428, compound

Product 1

HCID 68325408HCID 68325408, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (S)-2-[4-(4-chloro-phenylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl ester (60 mg) in DMF (2 ml) was added sodium hydride (6.2 mg) and stirring was continued at room temperature for 15 min. Iodomethane (24.3 mg) was then added dropwise. The reaction mixture was stirred at room temperature for 1 h. TLC at t=1 h showed the reaction was incomplete with some starting material remaining A second portion of sodium hydride (6.2 mg) was added. After stirring at room temperature for 15 min, iodomethane (24.3 mg) was added. Stirring was continued for a further hour. TLC then showed the reaction was complete. The reaction mixture was poured into sat. aq. NaCl and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in heptane) to afford (S)-2-{4-[(4-chloro-phenyl)-methyl-amino]-phenyl}-morpholine-4-carboxylic acid tert-butyl ester (49 mg, 79%) as a colourless gum. MS (ISP): 405.4 ([{37Cl}M+H]+), 403.4 ([{35Cl}M+H]+).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 1 h
  2. customat t=1 h
  3. additionwas added
  4. stirringAfter stirring at room temperature for 15 min
  5. stirringStirring
  6. waitwas continued for a further hour
  7. extractionextracted twice with EtOAc
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-c158e4134fcb40ab989a157a6deb5cbe
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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