Methanol → 2-(8-(Benzyloxycarbonyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)benzoic acid

HRID 1751129Notes

Reaction equation

HRID 1751129 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[C:15](=[O:16])[C:14]2([CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[O:23])[CH2:18][CH2:17]2)[N:13]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:12]1)=[O:4].[OH-].[Li+].CO.O>O1CCOCC1>[CH2:25]([O:24][C:22]([N:19]1[CH2:18][CH2:17][C:14]2([N:13]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:12][N:11]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[C:3]([OH:4])=[O:2])[C:15]2=[O:16])[CH2:21][CH2:20]1)=[O:23])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 66652584Benzyl 3-(2-(methoxycarbonyl)phenyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate

Product 1

HCID 580466472-(8-(Benzyloxycarbonyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)benzoic acidYield 99.9%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of benzyl 3-(2-(methoxycarbonyl)phenyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate (2.35 g, 4.7 mmol, 1 equiv.) and lithium hydroxide (394.4 mg, 9.4 mmol, 2 equiv) in a 3:1 mixture of methanol and water (20 ml t/v) was stirred at 60° C. for 16 hrs. Some dioxane was added to remove the turbidity in the reaction mixture and the stirring was continued for another 20 h. The reaction was concentrated in vacuo and the residue was partitioned between ethyl acetate and 10% citric acid. The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated and dried in vacuo to afford the title compound as a cream solid (2.28 g, quant); 1H NMR (400 MHz, DMSO-d6): δ 1.88 (d, 2H, J=14 Hz); 2.38-2.45 (m, 2H); 3.52 (bs, 2H); 3.97-4.05 (m, 2H); 5.08 (s, 2H); 5.15 (d, 2H, J=16.4 Hz); 6.79-6.84 (m, 3H); 7.20-7.24 (m, 2H); 7.33-7.39 (m, 5H); 7.49-7.53 (m, 1H); 7.61 (dd, 1H, J=0.8 Hz); 7.68-7.72 (m, 1H); 791 (dd, 1H, J=1.6 Hz); 13.1 (bs, 1H); MS for C28H27N3O5 m/z 486.3 (M+H)+.

Workup

  1. customto remove the turbidity in the reaction mixture
  2. waitthe stirring was continued for another 20 h
  3. concentrationThe reaction was concentrated in vacuo
  4. customthe residue was partitioned between ethyl acetate and 10% citric acid
  5. washThe organic layer was washed with water and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customdried in vacuo

Sources & evidence

ORD record
ord-017e0a6a48b14914a9127936de0fecbd
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

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