Ammonium Chloride → HCID 21070520, compound

HRID 1371731Notes

Reaction equation

HRID 1371731 reaction equation
Br[C:2]1[C:3]([Cl:9])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[C:15]([Si:19]([CH3:34])([CH3:33])[O:20][C:21]1[C:22]([O:31][CH3:32])=[C:23]([C:26]([F:30])=[C:27]([F:29])[CH:28]=1)[CH:24]=[O:25])([CH3:18])([CH3:17])[CH3:16].[Cl-].[NH4+]>O1CCCC1.O.C(OCC)(=O)C>[C:15]([Si:19]([CH3:34])([CH3:33])[O:20][C:21]1[C:22]([O:31][CH3:32])=[C:23]([CH:24]([C:2]2[C:3]([Cl:9])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=2)[OH:25])[C:26]([F:30])=[C:27]([F:29])[CH:28]=1)([CH3:18])([CH3:17])[CH3:16]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 2899735-Bromo-2,4-dichloropyrimidineHCID 21070519HCID 21070519, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 21070520HCID 21070520, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-30 °C

Procedure

To a solution of 5-bromo-2,4-dichloropyrimidine (753.6 mg, 3.307 mmol, Matrix Chemicals) in tetrahydrofuran (20 mL) cooled to −30° C. was added dropwise isopropylmagnesium chloride. The temperature was maintained below −25° C. throughout the addition. At the end of addition, the reaction mixture was stirred at −30° C. for 20 minutes and a solution of 3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-benzaldehyde (1 g, 3.307 mmol, Example 266) in tetrahydrofuran was added dropwise. The temperature was maintained below −25° C. throughout the addition. The reaction mixture was allowed to warm up to 0° C. after the addition was completed. After being stirred at 0° C. for 45 minutes, saturated solution of ammonium chloride (−3 mL) was added. The mixture was taken up in water and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over anhydrous magnesium sulfate. The solids were filtered off and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, 60 Å silica gel, eluting with 5–10% ethyl acetate in hexanes) yielded [3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-phenyl]-(2,4-dichloro-pyrimidin-5-yl)-methanol as white solids (965 mg, 65%). LR-MS (M+) 451.1.

Workup

  1. temperatureThe temperature was maintained below −25° C. throughout the addition
  2. additionAt the end of addition
  3. temperatureThe temperature was maintained below −25° C. throughout the addition
  4. temperatureto warm up to 0° C.
  5. additionafter the addition
  6. stirringAfter being stirred at 0° C. for 45 minutes
  7. extractionThe aqueous layer was extracted with ethyl acetate
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationThe solids were filtered off
  11. concentrationthe filtrate was concentrated in vacuo
  12. customPurification of the crude residue
  13. washby flash chromatography (Biotage system, 60 Å silica gel, eluting with 5–10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3f64164ab88e40a1828a7b7a9253cece
Source dataset
uspto-grants-2007_01
Patent number
US07157455B2

Reaction notes

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