Hydrochloric Acid → 2-{[(1,1-dimethylethyl)oxy]carbonyl}-6-{N-[(methyloxy)carbonyl]-L-valyl}-2,6-diazaspiro[3,4]octane-7-carboxylic acid

HRID 1800790Notes

Reaction equation

HRID 1800790 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:10]([N:12]1[CH:26]([C:27]([O:29]CC)=[O:28])[CH2:25][C:14]2([CH2:17][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:15]2)[CH2:13]1)=[O:11])[CH:7]([CH3:9])[CH3:8])=[O:4].O.[OH-].[Li+].Cl>C1COCC1.O.CO>[CH3:24][C:21]([O:20][C:18]([N:16]1[CH2:15][C:14]2([CH2:25][CH:26]([C:27]([OH:29])=[O:28])[N:12]([C:10](=[O:11])[C@H:6]([CH:7]([CH3:8])[CH3:9])[NH:5][C:3]([O:2][CH3:1])=[O:4])[CH2:13]2)[CH2:17]1)=[O:19])([CH3:22])[CH3:23]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 583130532-(1,1-dimethylethyl) 7-ethyl 6-{N-[(methyloxy)carbonyl]-L-valyl}-2,6-diazaspiro[3,4]octane-2,7-dicarboxylate

Product 1

HCID 583130782-{[(1,1-dimethylethyl)oxy]carbonyl}-6-{N-[(methyloxy)carbonyl]-L-valyl}-2,6-diazaspiro[3,4]octane-7-carboxylic acidYield 76%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a solution of 2-(1,1-dimethylethyl) 7-ethyl 6-{N-[(methyloxy)carbonyl]-L-valyl}-2,6-diazaspiro[3.4]octane-2,7-dicarboxylate (146) (344 mg, 0.78 mmol) in THF/water/methanol (3 mL/1.5 mL/1.5 mL) was added lithium hydroxide monohydrate (65 mg, 1.56 mmol) and the reaction stirred at room temperature for 1.5 h whereupon it was treated with 1N HCl (1.5 mL). The reaction was partitioned between EtOAc and water (30 mL each), the aqueous layer was extracted with EtOAc (30 mL), the organic layers were combined and dried (MgSO4) and concentrated in vacuo to afford the title compound as a white solid (245 mg, 76% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.46 (br. s., 1H) 7.06-7.66 (m, 1H) 4.13-4.32 (m, 1H) 3.88-4.12 (m, 2H) 3.56-3.89 (m, 5H) 3.39-3.57 (m, 3H) 2.24-2.45 (m, 1H) 1.99-2.19 (m, 1H) 1.80-1.95 (m, 1H) 1.26-1.44 (m, 9H) 0.56-1.00 (m, 6H). LC-MS ESI (M−H)−=412.41.

Workup

  1. customThe reaction was partitioned between EtOAc and water (30 mL each)
  2. extractionthe aqueous layer was extracted with EtOAc (30 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d68490d38490445cba0a319072e572d4
Source dataset
uspto-grants-2013_01
Patent number
US08344155B2

Reaction notes

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