Acetic Acid → 4-{[(2,4-Dichloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid t-butyl ester

HRID 2111935Notes

Reaction equation

HRID 2111935 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH2:28])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[Cl:29][C:30]1[S:31][C:32]([CH:36]=O)=[C:33]([Cl:35])[N:34]=1.C(O)(=O)C.[OH-].[Na+]>ClCCCl>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH:28][CH2:36][C:32]2[S:31][C:30]([Cl:29])=[N:34][C:33]=2[Cl:35])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 12682914-Amino-1-Boc-piperidineHCID 14886722,4-Dichloro-1,3-thiazole-5-carboxaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 685747814-{[(2,4-Dichloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid t-butyl esterYield 62.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Add sodium triacetoxyborohydride (1.70 g, 8.02 mmol) to a stirred solution of 4-amino-piperidine-1-carboxylic acid tert-butyl ester (1.0124 g, 5.06 mmol), 2,4-dichloro-thiazole-5-carbaldehyde (1.0113 g, 5.56 mmol), glacial acetic acid (0.31 mL, 5.42 mmol), and 1,2-dichloroethane (40 mL). Stir for 18 hours under nitrogen at room temperature. Pour the reaction into 2N NaOH (100 mL) and extract with ethyl acetate (3×100 mL). Dry the ethyl acetate over sodium sulfate and then filter off the sodium sulfate. Concentrate on a rotary evaporator and purify the crude product by flash chromatography on silica gel eluting with 35% ethyl acetate/hexanes then with 100% ethyl acetate to yield 1.1547 g (62%) of 4-{[(2,4-dichloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=366.1 (M+1); 1H NMR (CDCl3): δ=4.04 (br s, 2H), 3.96 (s, 2H), 2.87-2.81 (m, 2H), 2.72-2.65 (m, 1H), 1.90-1.86 (m, 2H), 1.48-1.39 (m, 10H), 1.33-1.23 (m, 2H).

Workup

  1. additionPour
  2. extractionextract with ethyl acetate (3×100 mL)
  3. dry with materialDry the ethyl acetate over sodium sulfate
  4. filtrationfilter off the sodium sulfate
  5. concentrationConcentrate on a rotary evaporator
  6. custompurify the crude product by flash chromatography on silica gel eluting with 35% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-a62009e8ae534594b65a2cbba8c7cedd
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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