Acetic Acid → 1,1-Dimethylethyl 4-(2-thiazolylamino)-1-piperidinecarboxylate

HRID 1880645Notes

Reaction equation

HRID 1880645 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.N[CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>C1COCC1>[C:17]([O:16][C:14]([N:11]1[CH2:12][CH2:13][CH:8]([NH:1][C:2]2[S:3][CH:4]=[CH:5][N:6]=2)[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:18])[CH3:19]

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 21552-AminothiazoleHCID 12682914-Amino-1-Boc-piperidineHCID 5049666Sodium triacetoxyborohydride2×

Product 1

HCID 231309421,1-Dimethylethyl 4-(2-thiazolylamino)-1-piperidinecarboxylateYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 5.0 g (50 mmol) 2-aminothiazole, 10.0 g (50 mmol) tert-butyl 4-aminopiperidine-1-carboxylate, 21.2 g (100 mmol) sodium triacetoxyborohydride and 5.7 ml (100 mmol) acetic acid in THF (100 ml) was stirred for 24 h at RT. Subsequently, a further 10.6 g (50 mmol) sodium triacetoxyborohydride and 2.85 ml (50 mmol) acetic acid were added and stirring took place for a further 2 d at RT. The solvent was removed in vacuo and the residue was taken up by chloroform and washed a plurality of times with 10% aq. NaOH soln and water. The organic phase was dried over MgSO4, filtered, and concentrated in vacuo. Column chromatography (SiO2, Chloroform/EtOH 20:1) was carried out on the residue, yielding 712 mg (2.5 mmol, 25%) tert-butyl-4-(thiazol-2-ylamino)piperidine-1-carboxylate.

Workup

  1. stirringstirring
  2. customfor a further 2 d
  3. customat RT
  4. customThe solvent was removed in vacuo
  5. washwashed a plurality of times with 10% aq. NaOH soln
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-431f944866f1479a92482ac27dbcb84d
Source dataset
uspto-grants-2012_11
Patent number
US08318774B2

Reaction notes

Loading…