Acetic Acid → 4-{[(4-Chloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 2111931Notes

Reaction equation

HRID 2111931 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH2:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1.[Cl:29][C:30]1[N:31]=[CH:32][S:33][C:34]=1[CH:35]=O.C(O)(=O)C.[OH-].[Na+]>ClCCCl>[C:25]([O:24][C:22]([N:19]1[CH2:18][CH2:17][CH:16]([NH:15][CH2:35][C:34]2[S:33][CH:32]=[N:31][C:30]=2[Cl:29])[CH2:21][CH2:20]1)=[O:23])([CH3:28])([CH3:27])[CH3:26]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 12682914-Amino-1-Boc-piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 145013174-Chloro-1,3-thiazole-5-carbaldehyde

Product 1

HCID 685747514-{[(4-Chloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Add sodium triacetoxyborohydride (30.50 g, 144 mmol) to a stirred solution of 4-amino-1-N-Boc-piperidine (18.00 g, 89.9 mmol), 4-chloro-thiazole-5-carbaldehyde (13.09 g, 88.7 mmol), acetic acid (5.5 mL, 96.1 mmol), and 1,2-dichloroethane (350 mL). Stir the reaction for 18 hours at room temperature under nitrogen. Pour the reaction into 2N NaOH (400 mL) and extract with ethyl acetate (3×150 mL). Wash the ethyl acetate with brine (2×150 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 75% ethyl acetate/hexanes then with 100% ethyl acetate to yield 21.78 g (74%) of 4-{[(4-chloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=332.1 (M+1); 1H NMR (CDCl3): δ=8.67 (s, 1H), 4.10-4.02 (m, 4H), 2.88-2.82 (m, 2H), 2.74-2.67 (m, 1H), 1.92-1.89 (m, 2H), 1.49 (s, 9H), 1.37-1.28 (m, 3H).

Workup

  1. customthe reaction for 18 hours at room temperature under nitrogen
  2. additionPour
  3. extractionextract with ethyl acetate (3×150 mL)
  4. washWash the ethyl acetate with brine (2×150 mL)
  5. dry with materialDry the ethyl acetate over sodium sulfate
  6. filtrationfilter off the sodium sulfate
  7. concentrationConcentrate on a rotary evaporator
  8. custompurify the crude product by flash chromatography on silica gel eluting with 75% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-e129e425cc2c45b09deca7a25404f9a4
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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