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

HRID 2111932Notes

Reaction equation

HRID 2111932 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]([NH:28][CH2:29][C:30]2[S:34][CH:33]=[N:32][C:31]=2[Cl:35])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[CH:36](=O)[CH:37]([CH3:39])[CH3:38].C(O)(=O)C.[OH-].[Na+]>ClCCCl>[C:15]([O:19][C:20]([N:22]1[CH2:23][CH2:24][CH:25]([N:28]([CH2:29][C:30]2[S:34][CH:33]=[N:32][C:31]=2[Cl:35])[CH2:36][CH:37]([CH3:39])[CH3:38])[CH2:26][CH2:27]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 6561IsobutyraldehydeHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 685747514-{[(4-Chloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 685750414-{[(4-Chloro-thiazol-5-yl)methyl]-isobutyl-amino}-piperidine-1-carboxylic acid tert-butyl esterYield 97%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Add sodium triacetoxyborohydride (24.00 g, 113 mmol) to a stirred solution of 4-{[(4-chloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (21.78 g, 65.6 mmol), isobutyraldehyde (9.0 mL, 99.1 mmol), acetic acid (4.0 mL, 69.9 mmol), and 1,2-dichloroethane (260 mL). Stir the reaction for 18 hours at room temperature under nitrogen. Pour the reaction into 2N NaOH (300 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 25% ethyl acetate/hexanes to yield 24.67 g (97%) of 4-{[(4-chloro-thiazol-5-yl)methyl]-isobutyl-amino}-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=388.2 (M+1); 1H NMR (CDCl3): δ=8.65 (s, 1H), 4.21 (br s, 2H), 3.80 (s, 2H), 2.63-2.56 (m, 3H), 2.29 (d, 2H), 1.77-1.65 (m, 3H), 1.50-1.41 (m, 11H), 0.92 (d, 6H).

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 25% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-27016bac5f654a6ea756435170dd1575
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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