Sodium Hydroxide → 6-(tert-Butoxycarbonyl)-6-azaspiro[2.5]octane-1-carboxylic acid

HRID 520331Notes

Reaction equation

[CH:1]1([C:16]([O:18]CC)=[O:17])[C:3]2([CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]2)[CH2:2]1.[OH-].[Na+]>C(O)C.O>[C:12]([O:11][C:9]([N:6]1[CH2:5][CH2:4][C:3]2([CH:1]([C:16]([OH:18])=[O:17])[CH2:2]2)[CH2:8][CH2:7]1)=[O:10])([CH3:15])([CH3:13])[CH3:14]

Participants

Conditions

Temperature: 15 °C

Procedure

To the solution of 165c (500 mg, 1.76 mmol) in ethanol (8 mL) was added sodium hydroxide (212 mg, 5.3 mmol) in water (4 mL). See FIG. 6. The mixture was stirred at 15° C. for 12 h. The solvent was evaporated under reduced pressure. The aqueous solution was acidified with dilute hydrochloride acid (0.5 M) slowly under ice bath until pH˜4, and extracted with EtOAc (10 mL×3). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated to give 6-(tert-butoxycarbonyl)-6-azaspiro[2.5]octane-1-carboxylic acid 165d (390 mg, 83%) as a white solid. 1H NMR (400 MHz, CDCl3): δ 3.52-3.42 (m, 3H), 3.38-3.35 (m, 1H), 1.75-1.72 (m, 2H), 1.58-1.56 (m, 1H), 1.46-1.43 (m, 11H), 1.23-1.21 (m, 1H), 1.02-1.01 (m, 1H).

Workup

customThe solvent was evaporated under reduced pressure
customThe aqueous solution was acidified with dilute hydrochloride acid (0.5 M) slowly under ice bath until pH˜4
extractionextracted with EtOAc (10 mL×3)
dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-63dda7ce40584841905cdf810e586913
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09326985B2

Reaction notes

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