Acetic Acid → Methyl 1-{[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylate

HRID 1942659Notes

Reaction equation

HRID 1942659 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:13][C:14]([C:17]3[C:18]([CH2:25][CH3:26])=[C:19]([CH:22]=[CH:23][CH:24]=3)[CH:20]=O)=[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:36]1[CH2:39][CH:38]([C:40]([O:42][CH3:43])=[O:41])[CH2:37]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]([CH2:25][CH3:26])=[C:19]([CH2:20][N:36]4[CH2:39][CH:38]([C:40]([O:42][CH3:43])=[O:41])[CH2:37]4)[CH:22]=[CH:23][CH:24]=3)=[CH:15][N:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 517045Sodium AcetateHCID 20132751Methyl azetidine-3-carboxylateHCID 584940933-(2-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylbenzaldehyde

Product 1

HCID 58494061Methyl 1-{[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylateYield 149.8%

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-ethylbenzaldehyde (D74) (120 mg), acetic acid (0.022 mL) and sodium acetate (31.9 mg) in ethanol (20.00 mL) stirred under nitrogen at room temperature was added methyl 3-azetidinecarboxylate (90 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 (137 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 methyl 1-{[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylate (D88) (226 mg) as a brown oil. The crude product was used for next step without further purification. MS (ES): C26H29ClN2O3S requires 484. found 485.2 (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 (137 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-614826978f9a482fa46fbc004de4baf2
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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