Hydrochloric Acid → 8-{[(1,1-dimethylethyl)oxy]carbonyl}-2-{N-[(methyloxy)carbonyl]-L-valyl}-2,8-diazaspiro[4.5]decane-3-carboxylic acid

HRID 454433Notes

Reaction equation

HRID 454433 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:10]([N:12]1[CH:16]([C:17]([O:19]CC)=[O:18])[CH2:15][C:14]2([CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)[CH2:13]1)=[O:11])[CH:7]([CH3:9])[CH3:8])=[O:4].O.[OH-].[Li+].Cl>C1COCC1.O.CO>[CH3:31][C:30]([O:29][C:27]([N:24]1[CH2:23][CH2:22][C:14]2([CH2:13][N:12]([C:10](=[O:11])[C@H:6]([CH:7]([CH3:9])[CH3:8])[NH:5][C:3]([O:2][CH3:1])=[O:4])[CH:16]([C:17]([OH:19])=[O:18])[CH2:15]2)[CH2:26][CH2:25]1)=[O:28])([CH3:33])[CH3:32]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 583131578-(1,1-dimethylethyl) 3-ethyl 2-{N-[(methyloxy)carbonyl]-L-valyl}-2,8-diazaspiro[4.5]decane-3,8-dicarboxylate

Product 1

HCID 583130918-{[(1,1-dimethylethyl)oxy]carbonyl}-2-{N-[(methyloxy)carbonyl]-L-valyl}-2,8-diazaspiro[4.5]decane-3-carboxylic acidYield 91%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a solution of 8-(1,1-dimethylethyl) 3-ethyl 2-{N-[(methyloxy)carbonyl]-L-valyl}-2,8-diazaspiro[4.5]decane-3,8-dicarboxylate (132) (125 mg, 0.27 mmol) in THF/water/MeOH (1.2 mL/0.6 mL/0.6 mL) was added lithium hydroxide monohydrate (22 mg, 0.53 mmol) and the reaction stirred at room temperature for 1.5 h. The reaction was treated with 1N HCl (0.5 mL) and partitioned between EtOAc and 0.1 N HCl (10 mL each) and the aqueous layer extracted with EtOAc (10 mL). The organic layers were combined and dried (MgSO4) and concentrated in vacuo to afford the title compound as a white solid (107 mg, 91% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.29-12.54 (m, 1H) 7.08-7.44 (m, 1H) 4.47 (t, J=5.4 Hz, 1H) 4.13-4.30 (m, 1H) 3.86-4.13 (m, 3H) 3.45-3.58 (m, 3H) 3.16-3.27 (m, 2H) 2.64 (br. s., 1H) 2.15-2.31 (m, 1H) 1.81-1.95 (m, 1H) 1.43-1.67 (m, 3H) 1.29-1.43 (m, 11H) 0.69-1.03 (m, 6H). LC-MS ESI (M−H)−=440.59.

Workup

  1. custompartitioned between EtOAc and 0.1 N HCl (10 mL each)
  2. extractionthe aqueous layer extracted with EtOAc (10 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d2dab22b824b4b7abd14356b301b8275
Source dataset
uspto-grants-2013_07
Patent number
US08492554B2

Reaction notes

Loading…