Water → (1-{[4-(4-Bromophenyl)-1,3-thiazol-2-yl]amino}cyclobutyl)methanol

HRID 1436381Notes

Reaction equation

HRID 1436381 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:15]=[C:16]([NH:19][C:20]3([C:24](OCC)=[O:25])[CH2:23][CH2:22][CH2:21]3)[S:17][CH:18]=2)=[CH:10][CH:9]=1.O.[OH-].[Na+]>O1CCCC1>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[N:15]=[C:16]([NH:19][C:20]3([CH2:24][OH:25])[CH2:23][CH2:22][CH2:21]3)[S:17][CH:18]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 86618583Ethyl 1-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}cyclobutane carboxylate

Product 1

HCID 86618584(1-{[4-(4-Bromophenyl)-1,3-thiazol-2-yl]amino}cyclobutyl)methanolYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium aluminum hydride (290 mg, 7.6 mmol) was added under nitrogen in portions to a solution of ethyl 1-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}cyclobutane carboxylate (990 mg, 2.6 mmol), prepared in the previous step, in 15 mL of tetrahydrofuran at ice bath temperature. After the addition, the reaction was stirred at ice bath temperature for 3 h. Water (290 μL) was added dropwise, followed by the addition of 290 μL of 15% NaOH and then 870 μL of water. After the addition, the reaction was stirred for 40 min. The reaction was filtered through the Celite™ reagent and the Celite™ reagent washed with ethyl acetate. The filtrate was partitioned with water. The organic layer was separated, washed one time with water, one time with saturated sodium chloride, dried (MgSO4), filtered and the solvent removed under reduced pressure. Purification of the residue on a Horizon™ Flash Collector (the Biotage FLASH 40+™ cartridge) using a linear gradient of ethyl acetate in methylene chloride gave (1-{[4-(4-bromophenyl)-1,3-thiazol-2-yl]amino}cyclobutyl)methanol (483 mg, 55%) as a light yellow solid, MS (ESI) m/z 339 [M+H]+.

Workup

  1. additionAfter the addition
  2. additionAfter the addition
  3. stirringthe reaction was stirred for 40 min
  4. filtrationThe reaction was filtered through the Celite™ reagent
  5. washthe Celite™ reagent washed with ethyl acetate
  6. customThe filtrate was partitioned with water
  7. customThe organic layer was separated
  8. washwashed one time with water, one time with saturated sodium chloride
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customthe solvent removed under reduced pressure
  12. customPurification of the residue on a Horizon™ Flash Collector (the Biotage FLASH 40+™ cartridge)

Sources & evidence

ORD record
ord-0b7f36240b4e40449ed61f13d2e50aaf
Source dataset
uspto-grants-2009_11
Patent number
US07618990B2

Reaction notes

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