Aluminium lithium hydride → (1-{[4-(4-Bromophenyl)-1,3-thiazol-2-yl]amino}cyclopropyl)methanol

HRID 1436378Notes

Reaction equation

HRID 1436378 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([NH:13][C:14]3([C:17](OCC)=[O:18])[CH2:16][CH2:15]3)[S:11][CH:12]=2)=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]([NH:13][C:14]3([CH2:17][OH:18])[CH2:15][CH2:16]3)[S:11][CH:12]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86618581Ethyl 1-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}cyclopropane carboxylate

Product 1

HCID 86618582(1-{[4-(4-Bromophenyl)-1,3-thiazol-2-yl]amino}cyclopropyl)methanolYield 14.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of ethyl 1-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}cyclopropane carboxylate (3.91 g, 10.6 mmol), prepared in the previous step, in 50 mL of anhydrous tetrahydrofuran was added under nitrogen dropwise to a suspension of lithium aluminum hydride (1.00 g, 26.3 mmol) in 20 mL of anhydrous tetrahydrofuran at ice-bath temperature. After the addition, the cooling bath was removed and the stirring continued for 1 h. Water (1 mL) was slowly added to the reaction, followed by the addition of 1 mL of 15% NaOH and then 3 mL of water. After the additions, the reaction was stirred for 1 h. The reaction was diluted with ethyl acetate and filtered through the Celite™ reagent. The filtrate was extracted two times with water, dried (anhydrous MgSO4), filtered and the solvent removed under reduced pressure to give a crude residue. The residue was taken up in methylene chloride, applied to a Biotage FLASH 40+™ cartridge and the methylene chloride allowed to evaporate. Purification of the residue on the samplet on a Horizon™ Flash Collector (the Biotage FLASH 40+™ cartridge) using a linear gradient of 5% methylene chloride-hexane to 100% methylene chloride gave a material which was recrystallized from methylene chloride to give (1-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}cyclopropyl)methanol (0.4867 g, 14%) as a white solid mp 129-131° C.; MS (ES) m/z 324.9.

Workup

  1. additionAfter the addition
  2. customthe cooling bath was removed
  3. additionWater (1 mL) was slowly added to the reaction
  4. additionfollowed by the addition of 1 mL of 15% NaOH
  5. additionThe reaction was diluted with ethyl acetate
  6. filtrationfiltered through the Celite™ reagent
  7. extractionThe filtrate was extracted two times with water
  8. dry with materialdried (anhydrous MgSO4)
  9. filtrationfiltered
  10. customthe solvent removed under reduced pressure
  11. customto give a crude residue
  12. customto evaporate
  13. customPurification of the residue on the samplet on a Horizon™ Flash Collector (the Biotage FLASH 40+™ cartridge)
  14. customgave a material which
  15. customwas recrystallized from methylene chloride

Sources & evidence

ORD record
ord-e4a24b9fb7d5484f9c675aaee037237e
Source dataset
uspto-grants-2009_11
Patent number
US07618990B2

Reaction notes

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