1,2-Dichloroethane → [(R)-2-(3,3-difluoro-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester
Reaction equation
[C:1]([NH:8][C@@H:9]([C:11]([OH:13])=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.[F:15][C:16]1([F:20])[CH2:19][NH:18][CH2:17]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:4]([O:3][C:1](=[O:2])[NH:8][C@H:9]([CH3:10])[C:11]([N:18]1[CH2:19][C:16]([F:20])([F:15])[CH2:17]1)=[O:13])([CH3:5])([CH3:6])[CH3:7]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
A round-bottomed flask was charged with Boc-D-alanine (400 mg, 2.11 mmol), 3,3-difluoroazetidine hydrochloride (383 mg, 2.96 mmol), HOBT (356 mg, 2.33 mmol) and EDC (446 mg, 2.33 mmol). DMF (9 ml) was added followed by N,N-diisopropylethylamine (1.0 ml, 5.73 mmol). The reaction mixture was stirred at room temperature for 48 h then quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated to give 509 mg (91%) of [(R)-2-(3,3-difluoro-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester as a light yellow solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 5.14 (d, J=7.2 Hz, 1H), 4.59-4.80 (m, 1H), 4.17-4.55 (m, 4H), 1.45 (s, 9H), 1.32 (d, J=7.2 Hz, 3H).
Workup
- customthen quenched with water
- extractionextracted with diethyl ether (2×)
- washThe combined organic layers were washed twice with water and once with brine
- dry with materialthen dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-6e00e4ba06c848d1bbab9b4d9e1bbb96
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08658646B2
Reaction notes
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