Carbon Dioxide → (1R,5R)-3,5,8,8-Tetramethyl-2,4-dioxo-3-azabicyclo[3.2.1]octane-1-carboxylic acid

HRID 1258120Notes

Reaction equation

[CH3:1][C@:2]12[C:9]([CH3:11])([CH3:10])[CH:6]([CH2:7][CH2:8]1)[C:5](=[O:12])[N:4]([CH3:13])[C:3]2=[O:14].N[C@H](C(O)=O)C[SeH].[Li]CCCC.C1CCCCC1.[C:33](=[O:35])=[O:34]>C1COCC1>[CH3:13][N:4]1[C:3](=[O:14])[C@@:2]2([CH3:1])[C:9]([CH3:10])([CH3:11])[C@:6]([C:33]([OH:35])=[O:34])([CH2:7][CH2:8]2)[C:5]1=[O:12]

Participants

Conditions

Temperature: -95 °C

Procedure

To a solution of step 2 intermediate (2 g, 10.2 mmol) in THF maintained at −95° C. under N2 atmosphere, 1.2N Sec.BuLi in cyclohexane (9.5 mL, 13.3 mmol) was added. After stirring for 15 min at −95° C., small pieces of dry ice (2 g) were added and the reaction mixture was kept at this temperature for 1 h before quenching with water (3 mL). The reaction mixture was allowed to warm to room temperature. To this 5% NaHCO3 solution (100 mL) and diethyl ether (50 mL) was added, the aqueous layer was separated and acidified with KHSO4 to pH 2. This was extracted again with diethyl ether, washed with brine, dried with anhydrous Na2SO4 and concentrated. (1.85 g). 1H NMR (400 MHz, CDCl3) δ ppm: 1.0 (s, 3H), 1.1 (s, 3H), 1.26 (s, 3H), 1.88-1.98 (m, 2H), 2.64-2.72 (m, 1H), 2.8 (m, 1H), 3.13 (s, 3H). m/z (M−H): 238.

Workup

waitthe reaction mixture was kept at this temperature for 1 h
custombefore quenching with water (3 mL)
temperatureto warm to room temperature
additionTo this 5% NaHCO3 solution (100 mL) and diethyl ether (50 mL) was added
customthe aqueous layer was separated
extractionThis was extracted again with diethyl ether
washwashed with brine
dry with materialdried with anhydrous Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-9c9e73429ac34d2d8fa123b4383a11c9
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08466145B2

Reaction notes

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