Hydrochloric Acid → 1-(tert-Butoxycarbonyl)-3-[2-[2-(4-chlorophenyl)-4-methylthiazol-5-yl]-2-oxoethyl]piperidine

HRID 602192Notes

Reaction equation

HRID 602192 reaction equation
C([N-]C(C)C)(C)C.[Li+].CCCCCCC.O1CCCC1.C(C1C=CC=CC=1)C.[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[S:37][C:38]([CH:42]([O:45][Si](C)(C)C)[C:43]#N)=[C:39]([CH3:41])[N:40]=2)=[CH:32][CH:31]=1.[C:50]([O:54][C:55]([N:57]1[CH2:62][CH2:61][CH2:60][CH:59](CI)[CH2:58]1)=[O:56])([CH3:53])([CH3:52])[CH3:51].Cl>O1CCCC1>[C:50]([O:54][C:55]([N:57]1[CH2:62][CH2:61][CH2:60][CH:59]([CH2:43][C:42]([C:38]2[S:37][C:36]([C:33]3[CH:34]=[CH:35][C:30]([Cl:29])=[CH:31][CH:32]=3)=[N:40][C:39]=2[CH3:41])=[O:45])[CH2:58]1)=[O:56])([CH3:53])([CH3:51])[CH3:52]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 2724682Lithium diisopropylamideHCID 20716152Tert-butyl 3-(iodomethyl)piperidine-1-carboxylateHCID 22742125Tetrahydrofuran heptane ethylbenzolHCID 589926472-[2-(4-Chlorophenyl)-4-methylthiazol-5-yl]-2-(trimethylsilyloxy)acetonitrile

Product 1

HCID 589926751-(tert-Butoxycarbonyl)-3-[2-[2-(4-chlorophenyl)-4-methylthiazol-5-yl]-2-oxoethyl]piperidineYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In an argon atmosphere, a solution of 1.8 mol/L lithium diisopropylamide in heptane/tetrahydrofuran/ethylbenzene (1.22 mL, 2.19 mmol), chilled to −78° C., was added to 2-[2-(4-chlorophenyl)-4-methylthiazol-5-yl]-2-(trimethylsilyloxy)acetonitrile (669 mg, 1.99 mmol) in tetrahydrofuran (2 mL). The mixture was stirred for 20 min, followed by addition of 1-(tert-butoxycarbonyl)-3-iodomethylpiperidine (647 mg, 1.99 mmol) in tetrahydrofuran (2 mL). The mixture was further stirred for 1 hour as it warmed from −78° C. to room temperature. 0.5 mol/L ice-chilled hydrochloric acid was then added and the mixture was further stirred for 10 min. Subsequently, the mixture was extracted with ethyl acetate and washed sequentially with a saturated aqueous sodium bicarbonate solution and brine. The washed product was dried over magnesium sulfate and the solvent was evaporated. Purification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=20:1->5:1) gave 429 mg (50%) of the desired compound as a yellow oil.

Workup

  1. stirringThe mixture was further stirred for 1 hour as it
  2. temperaturewarmed from −78° C. to room temperature
  3. additionwas then added
  4. stirringthe mixture was further stirred for 10 min
  5. extractionSubsequently, the mixture was extracted with ethyl acetate
  6. washwashed sequentially with a saturated aqueous sodium bicarbonate solution and brine
  7. dry with materialThe washed product was dried over magnesium sulfate
  8. customthe solvent was evaporated
  9. customPurification of the resulting residue by silica gel column chromatography (hexane:ethyl acetate=20:1->5:1)

Sources & evidence

ORD record
ord-09a6fe3263884bb79ff248ffa0046b08
Source dataset
uspto-grants-2011_03
Patent number
US07902367B2

Reaction notes

Loading…