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

HRID 1942657Notes

Reaction equation

HRID 1942657 reaction equation
[CH2:1]([C:3]1[C:8]([CH2:9][CH:10]=O)=[CH:7][CH:6]=[CH:5][C:4]=1[C:12]1[S:16][C:15]([C:17]2[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=2)[C:22]#[N:23])=[N:14][CH:13]=1)[CH3:2].C(O)(=O)C.C([O-])(=O)C.[Na+].[NH:38]1[CH2:43][CH2:42][CH:41]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:40][CH2:39]1>C(O)C>[C:22]([C:21]1[CH:24]=[C:17]([C:15]2[S:16][C:12]([C:4]3[C:3]([CH2:1][CH3:2])=[C:8]([CH2:9][CH2:10][N:38]4[CH2:43][CH2:42][CH:41]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:40][CH2:39]4)[CH:7]=[CH:6][CH:5]=3)=[CH:13][N:14]=2)[CH:18]=[CH:19][C:20]=1[O:25][CH:26]([CH3:28])[CH3:27])#[N:23]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 70770Ethyl 4-piperidinecarboxylateHCID 517045Sodium AcetateHCID 866590085-{5-[2-Ethyl-3-(2-oxoethyl)phenyl]-1,3-thiazol-2-yl}-2-[(1-methylethyl)oxy]benzonitrile

Product 1

HCID 66981746Ethyl 1-{2-[3-(2-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylateYield 99.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 5-{5-[2-ethyl-3-(2-oxoethyl)phenyl]-1,3-thiazol-2-yl}-2-[(1-methylethyl)oxy]benzonitrile (D76) (150 mg), acetic acid (0.044 mL) and sodium acetate (63.0 mg) in ethanol (20.00 mL) stirred under nitrogen at room temperature was added ethyl 4-piperidinecarboxylate (181 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 (204 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-cyano-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate (D86) (204 mg) as a brown oil. The crude product was used for next step without further purification. MS (ES): C31H37N3O3S requires 531. found 532.3 (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 (204 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-b6a93809103c48be83994155af1f97e1
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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