Isobutylene oxide → 4-{[(2,4-Dichloro-thiazol-5-yl)methyl]-(2-hydroxy-2-methyl-propyl)-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 2111936Notes

Reaction equation

HRID 2111936 reaction equation
[CH3:1][C:2]1([CH3:5])[CH2:4][O:3]1.Cl([O-])(=O)(=O)=O.[Li+].[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH:25][CH2:26][C:27]2[S:31][C:30]([Cl:32])=[N:29][C:28]=2[Cl:33])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(=O)(O)[O-].[Na+]>C(#N)C>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([N:25]([CH2:26][C:27]2[S:31][C:30]([Cl:32])=[N:29][C:28]=2[Cl:33])[CH2:1][C:2]([OH:3])([CH3:5])[CH3:4])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

6

Reactant 4

HCID 11208Isobutylene oxideHCID 516892Sodium BicarbonateHCID 23665649Lithium perchlorateHCID 685747814-{[(2,4-Dichloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid t-butyl ester

Product 1

HCID 685774114-{[(2,4-Dichloro-thiazol-5-yl)methyl]-(2-hydroxy-2-methyl-propyl)-amino}-piperidine-1-carboxylic acid tert-butyl esterYield 33.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

Add 2,2-dimethyl-oxirane (3.0 mL, 33.3 mmol) to a stirred suspension of lithium perchlorate (3.39 g, 31.9 mmol) in anhydrous acetonitrile (40 mL). Stir for one hour under nitrogen at room temperature. Add 4-{[(2,4-dichloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (1.1337 g, 3.10 mmol) in anhydrous acetonitrile (15 mL). Heat the reaction at reflux for 72 hours under nitrogen. Pour the reaction into saturated sodium bicarbonate (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 30% ethyl acetate/hexanes to yield 0.4527 g (33%) of 4-{[(2,4-dichloro-thiazol-5-yl)methyl]-(2-hydroxy-2-methyl-propyl)-amino}-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=438.2 (M+1); 1H NMR (CDCl3): δ=4.22 (br s, 2H), 3.97 (s, 2H), 2.67-2.59 (m, 3H), 2.50 (s, 2H), 1.77-1.74 (m, 2H), 1.60 (s, 2H), 1.49 (s, 9H), 1.47-1.35 (m, 1H), 1.23 (s, 6H).

Workup

  1. temperatureHeat
  2. customthe reaction
  3. temperatureat reflux for 72 hours under nitrogen
  4. additionPour
  5. extractionextract with ethyl acetate (3×100 mL)
  6. dry with materialDry the ethyl acetate over sodium sulfate
  7. filtrationfilter off the sodium sulfate
  8. concentrationConcentrate on a rotary evaporator
  9. custompurify the crude product by flash chromatography on silica gel eluting with 30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b8b90998318b4319b1a38f3e24761d41
Source dataset
uspto-grants-2009_04
Patent number
US07521462B2

Reaction notes

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