Methyl bromoacetate → (S)-methyl 2-(3-(tert-butoxycarbonylamino)-2-oxoazepan-1-yl)acetate
Reaction equation
[O:1]=[C:2]1[C@@H:8]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:7][CH2:6][CH2:5][CH2:4][NH:3]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:28][C:29]([O:31][CH3:32])=[O:30]>C1COCC1>[C:12]([O:11][C:10]([NH:9][C@H:8]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]([CH2:28][C:29]([O:31][CH3:32])=[O:30])[C:2]1=[O:1])=[O:16])([CH3:13])([CH3:15])[CH3:14]Participants
Procedure
To a round bottom flask was added (S)-tert-butyl 2-oxoazepan-3-ylcarbamate (130 mg, 0.569 mmol), THF (10 mL) and LiHMDS (0.190 mL, 1.14 mmol). The reaction was stirred at rt for 30 min. Then methyl 2-bromoacetate (0.079 mL, 0.85 mmol) was added to the reaction and the reaction mixture was stirred at rt overnight. The reaction mixture was concentrated and purified by RP prep-HPLC to give (S)-methyl 2-(3-(tert-butoxycarbonylamino)-2-oxoazepan-1-yl)acetate (60 mg, 0.20 mmol, 35% yield) as a clear oil. Anal. Calcd. for C14H24N2O5 m/z 300.3. found: 301.2 (M+H)+; 1H NMR (500 MHz, CDCl3) δ ppm 5.89 (br. s., 1H), 4.40 (d, J=4.4 Hz, 1H), 4.13 (br. s., 2H), 3.79-3.56 (m, 4H), 3.15 (d, J=12.1 Hz, 1H), 2.07-1.87 (m, 2H), 1.75 (d, J=10.4 Hz, 2H), 1.62-1.49 (m, 2H), 1.39 (br. s., 9H); 13C NMR (126 MHz, CDCl3) δ ppm 173.82, 169.55, 155.20, 79.55, 53.36, 52.17, 50.71, 50.63, 32.21, 28.31, 27.80, 26.87.
Workup
- stirringthe reaction mixture was stirred at rt overnight
- concentrationThe reaction mixture was concentrated
- custompurified by RP prep-HPLC
Sources & evidence
- ORD record
- ord-8956adb6660f4b02b3e7033389fe8495
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09346852B2
Reaction notes
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