1-Hydroxybenzotriazole → 1-[2-(3,5-Dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid ethyl ester
Reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=O)[CH:5]=[C:6]([CH3:8])[CH:7]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[CH2:36]([O:38][C:39]([C:41]1([CH3:45])[CH2:44][CH2:43][NH:42]1)=[O:40])[CH3:37]>C1COCC1.C(Cl)Cl>[CH2:36]([O:38][C:39]([C:41]1([CH3:45])[CH2:44][CH2:43][N:42]1[C:10](=[O:12])[CH2:9][C:4]1[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([CH3:1])[CH:3]=1)=[O:40])[CH3:37]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 20 °C
Procedure
To a solution of (3,5-dimethyl-phenyl)-acetic acid (1 eq.) in either DCM or THF was added HOBt (1.1 eq.), EDC.HCl (1.5 eq.). Then, 2-methyl-azetidine-2-carboxylic acid ethyl ester hydrochloride, Intermediate 13 (1 eq.) and TEA (4 eq.) were added. The reaction was stirred at 20° C. for 15 h. The crude was concentrated under reduced pressure and partitioned between a saturated aqueous solution of NaHCO3 and EtOAc. The aqueous layer was extracted three times with EtOAc. The organic layers were combined, washed with water then with brine, dried over MgSO4, filtered and concentrated under reduced pressure to afford 1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid ethyl ester.
Workup
- concentrationThe crude was concentrated under reduced pressure
- custompartitioned between a saturated aqueous solution of NaHCO3 and EtOAc
- extractionThe aqueous layer was extracted three times with EtOAc
- washwashed with water
- dry with materialwith brine, dried over MgSO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-3999b9e3803f46b0b40d0158630d6d13
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08759334B2
Reaction notes
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