1-Piperidinecarboxaldehyde → 2-Aminobenzo[d]thiazole-6-carbaldehyde

HRID 2252060Notes

Reaction equation

HRID 2252060 reaction equation
C1([Li])C=CC=CC=1.Br[C:9]1[S:10][C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=2[N:13]=1.C([Li])(C)(C)C.[CH:23](N1CCCCC1)=[O:24].[NH4+:31].[Cl-]>C1CCCCC1.CCOCC.C1COCC1.CCCCC>[NH2:31][C:9]1[S:10][C:11]2[CH:17]=[C:16]([CH:23]=[O:24])[CH:15]=[CH:14][C:12]=2[N:13]=1

Participants

9

Reactant 5

HCID 174291-PiperidinecarboxaldehydeHCID 25517Ammonium ChlorideHCID 6120402-Bromo-1,3-benzothiazoleHCID 178418306HCID 178418306, compoundHCID 178506676HCID 178506676, compound

Product 1

HCID 138215412-Aminobenzo[d]thiazole-6-carbaldehydeYield 50%

Reagents, catalysts & solvents 3

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolventHCID 21895417Cyclohexane diethyletherSolvent

Procedure

Under nitrogen atmosphere, slowly add phenyl lithium (5 mL, 9.16 mmol, 2.1 equiv from a solution 1.8 M in cyclohexane/ether, 70/30) to a cold (−78° C.) solution of commercially available 2-bromo benzothiazole in 30 mL of dry THF. After the addition is complete stir the mixture for 5 minutes and add t-butyl lithium (5.6 mL, 9.16 mmol, 2.1 equiv from a solution 1.7 M in pentane). The mixture will turn from a creamy white color to green over 1 hour. At this point, rapidly add formyl piperidine (2.4 mL, 21.8 mmol, 5 equiv) dropwise and warm the mixture slowly to (>1 hour) 0° C. Quench the reaction into a mixture of cold saturated NH4Cl and extract with EtOAc. Separate the phases and back extract the organic one with more EtOAc (three times). Dry the combined organic phases over MgSO4, filter and concentrate in vacuo to afford the ldehyde (50% yield).

Workup

  1. additionAfter the addition
  2. customgreen over 1 hour
  3. customQuench
  4. customthe reaction
  5. extractionextract with EtOAc
  6. customSeparate the phases
  7. extractionback extract the organic one with more EtOAc (three times)
  8. dry with materialDry the combined organic phases over MgSO4
  9. filtrationfilter
  10. concentrationconcentrate in vacuo
  11. customto afford the ldehyde (50% yield)

Sources & evidence

ORD record
ord-02d5c6e8328b424db75372d60da19326
Source dataset
uspto-grants-2008_01
Patent number
US07320995B2

Reaction notes

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