Acetic Acid → Ethyl 1-{2-[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate

HRID 1942660Notes

Reaction equation

HRID 1942660 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:13][C:14]([C:17]3[C:18]([CH2:26][CH3:27])=[C:19]([CH2:23][CH:24]=O)[CH:20]=[CH:21][CH:22]=3)=[CH:15][N:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C(O)(=O)C.C([O-])(=O)C.[Na+].[NH:37]1[CH2:42][CH2:41][CH:40]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:39][CH2:38]1>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:13][C:14]([C:17]3[C:18]([CH2:26][CH3:27])=[C:19]([CH2:23][CH2:24][N:37]4[CH2:42][CH2:41][CH:40]([C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH2:39][CH2:38]4)[CH:20]=[CH:21][CH:22]=3)=[CH:15][N:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 70770Ethyl 4-piperidinecarboxylateHCID 517045Sodium AcetateHCID 58494108[3-(2-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]acetaldehyde

Product 1

HCID 58494013Ethyl 1-{2-[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylateYield 99.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of [3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]acetaldehyde (D78) (160 mg), acetic acid (0.036 mL) and sodium acetate (51.0 mg) in ethanol (20.00 mL) stirred under nitrogen at room temperature was added ethyl 4-piperidinecarboxylate (189 mg) in one charge. The reaction mixture was stirred at room temperature for 30 min, then the solvent was evaporated in vacuo. The residue was dissolved in dichloromethane (DCM) (20 mL), sodium triacetoxyborohydride (165 mg) was added to the mixture. The reaction mixture was stirred at room temperature overnight. The reaction mixture was partitioned between ethyl acetate (100 mL) and saturated brine (30 mL). The organic phase was dried over sodium sulphate and evaporated in vacuo to give the crude product ethyl 1-{2-[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate (D89) (216 mg) as a brown oil. The crude product was used for next step without further purification. MS (ES): C30H37ClN2O3S requires 540. found 541.2 (M+H+).

Workup

  1. additioncharge
  2. customthe solvent was evaporated in vacuo
  3. dissolutionThe residue was dissolved in dichloromethane (DCM) (20 mL)
  4. additionsodium triacetoxyborohydride (165 mg) was added to the mixture
  5. stirringThe reaction mixture was stirred at room temperature overnight
  6. customThe reaction mixture was partitioned between ethyl acetate (100 mL) and saturated brine (30 mL)
  7. dry with materialThe organic phase was dried over sodium sulphate
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-d27529f9a2a3401486f43f07409b5aa4
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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