Pyridine → HCID 18378807, compound

HRID 2299018Notes

Reaction equation

HRID 2299018 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[N:10]=[CH:9]2)=[CH:4][C:3]=1[F:22].N1C=CC=CC=1.Cl[C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31]>ClCCl.C(=O)(O)[O-].[Na+]>[CH2:33]([O:32][C:30]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([CH2:13][O:14][Si:15]([C:18]([CH3:19])([CH3:21])[CH3:20])([CH3:16])[CH3:17])[N:10]=[CH:9]2)=[CH:4][C:3]=1[F:22])=[O:31])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 10387Benzyl chloroformateHCID 18378814HCID 18378814, compound

Product 1

HCID 18378807HCID 18378807, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
-20 °C

Procedure

1-Amino-4-(4-t-butyldimethylsilyloxymethylimidazol-1-yl)fluorobenzene (36.1 g) was dissolved in dry dichloromethane (450 ml), treated with pyridine (11.3 ml), then stirred under argon while cooling to −20° C. Benzyl chloroformate (17.7 ml) in dichioromethane (50 ml) was added dropwise, maintaining the temperature. The mixture was then allowed to warm to ambient temperature over 1 hour, then stirred for a further 1.5 hours. The mixture was diluted with aqueous sodium bicarbonate (250 ml), and the organic layer separated. A further extraction with dichloromethane (200 ml) was made, the combined organic layers dried over magnesium sulfate, and solvent evaporated. The resulting oil was re-evaporated with toluene, and purified by chromatography on silica (500 g) in a sinter column, eluting with a gradient from CH2Cl2 to 50% EtOAc in CH2Cl2. Evaporation, then re-evaporation with toluene gave solid product (51 g).

Workup

  1. temperaturemaintaining the temperature
  2. temperatureto warm to ambient temperature over 1 hour
  3. stirringstirred for a further 1.5 hours
  4. customthe organic layer separated
  5. extractionA further extraction with dichloromethane (200 ml)
  6. dry with materialthe combined organic layers dried over magnesium sulfate, and solvent
  7. customevaporated
  8. customThe resulting oil was re-evaporated with toluene
  9. custompurified by chromatography on silica (500 g) in a sinter column
  10. washeluting with a gradient from CH2Cl2 to 50% EtOAc in CH2Cl2
  11. customEvaporation
  12. customre-evaporation with toluene

Sources & evidence

ORD record
ord-056693a9a5f94db69f6f823904c05b45
Source dataset
uspto-grants-2002_12
Patent number
US06495551B1

Reaction notes

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