Ammonium Chloride → HCID 22020970, compound

HRID 1793323Notes

Reaction equation

HRID 1793323 reaction equation
[Cl:1][C:2]1[C:7](NC)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:10]([NH:13]C(C)C)(C)C.[Li].[C:18]1([CH2:24][O:25][CH2:26][CH:27]2[CH2:29][O:28]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[NH4+].[Cl-]>C1COCC1>[Cl:1][C:2]1[C:7]([CH2:10][NH:13][CH2:29][CH:27]([OH:28])[CH2:26][O:25][CH2:24][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 94247Benzyl glycidyl etherHCID 151641272-Chloro-N-methylpyridin-3-amineHCID 45051747Lithium diisopropylamine

Product 1

HCID 22020970HCID 22020970, compoundYield 75.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of intermediate (28) (0.031 mol) in THF (50 ml) under nitrogen flow at −78° C., lithium diisopropylamine (0.062 mol, 2 M) was slowly added. The reaction mixture was allowed to warm to 0° C. and was stirred for 1 hour. After cooling again to −78° C., a solution of [(phenylmethoxy)methyl]-oxirane (0.034 mol) in THF (40 ml) was added and the mixture was allowed to warm to room temperature and was stirred for 16 hours. A saturated NH4Cl-solution was added and the mixture was extracted with ethyl acetate. The separated organic layer was dried, filtered and the solvent was evaporated. The residue was purified by short open column chromatography over silica gel (eluent: hexane/ethyl acetate 50/50). The product fractions were collected and the solvent was evaporated, yielding 7.18 g of 1-[(2-chloro-3-pyridinyl)methylamino]-3-(phenylmethoxy)-2-propanol (intermediate 29).

Workup

  1. temperatureAfter cooling again to −78° C.
  2. temperatureto warm to room temperature
  3. stirringwas stirred for 16 hours
  4. extractionthe mixture was extracted with ethyl acetate
  5. customThe separated organic layer was dried
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customThe residue was purified by short open column chromatography over silica gel (eluent: hexane/ethyl acetate 50/50)
  9. customThe product fractions were collected
  10. customthe solvent was evaporated

Sources & evidence

ORD record
ord-1e3bc0647e1c48d681068c3311f015d4
Source dataset
uspto-grants-2006_07
Patent number
US07081453B2

Reaction notes

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