Sodium Bicarbonate → [(3S,6R)-6-(6-azido-hexyloxy)-1-methyl-2-oxo-azepan-3-yl]-carbamic acid tert-butyl ester

HRID 2224026Notes

Reaction equation

[C:1]([O:5][C:6](=[O:18])[NH:7][C@H:8]1[CH2:14][CH2:13][C@@H:12]([OH:15])[CH2:11][N:10]([CH3:16])[C:9]1=[O:17])([CH3:4])([CH3:3])[CH3:2].[N:19]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]OS(C(F)(F)F)(=O)=O)=[N+:20]=[N-:21].C([O-])(O)=O.[Na+]>C1COCC1>[C:1]([O:5][C:6](=[O:18])[NH:7][C@H:8]1[CH2:14][CH2:13][C@@H:12]([O:15][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][N:19]=[N+:20]=[N-:21])[CH2:11][N:10]([CH3:16])[C:9]1=[O:17])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: -78 °C

Procedure

To a stirred solution of ((3S,6R)-6-hydroxy-1-methyl-2-oxo-azepan-3-yl)-carbamic acid tert-butyl ester (0.70 g, 2.6 mmol) in THF (5 mL) cooled to −78° C. is added NaN(Si(CH3)3)2 (2.8 mL 1M THF, 2.8 mmol). After 10 min trifluoro-methanesulfonic acid 6-azido-hexyl ester (0.76 g, 3.1 mmol) is added neat and stirred for 10 min at −78° C. then warmed and stirred at room temperature for 1 h. NaHCO3 (5 mL 1M H2O) is added and the solution is partitioned with H2O/EtOAc, the EtOAc extract is dried with Na2SO4 and evaporated to an oil. The oil is adsorbed on silica and chromatographed (20% EtOAc/CH2Cl2) to give 0.32 g (32%) of [(3S,6R)-6-(6-azido-hexyloxy)-1-methyl-2-oxo-azepan-3-yl]-carbamic acid tert-butyl ester as an oil. 1H NMR (CDCl3) δ 1.34 (s, 9H), 1.24-2.1 (m, 12H), 2.95 (s, 3H), 3.1-3.35 (m, 6H), 3.44 (m, 1H), 3.55 (d, 1H), 4.2 (m, 1H).

Workup

temperaturethen warmed
stirringstirred at room temperature for 1 h
customthe solution is partitioned with H2O/EtOAc
extractionthe EtOAc extract
dry with materialis dried with Na2SO4
customevaporated to an oil
customchromatographed (20% EtOAc/CH2Cl2)

Sources & evidence

ORD record: ord-3025caed942f43849cbcb3c8ad2ead2c
Source dataset: uspto-grants-2008_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07378410B2

Reaction notes

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