Lithium Hydroxide → HCID 22507515, compound

HRID 985636Notes

Reaction equation

HRID 985636 reaction equation
C[O:2][C:3]([C:5]1([NH:11][C:12]([CH:14]2[CH2:18][CH:17]([O:19][C:20]3[C:29]4[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=4)[N:23]=[C:22]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:21]=3)[CH2:16][N:15]2[C:38](=[O:52])[CH:39]([NH:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[C:40]([CH3:43])([CH3:42])[CH3:41])=[O:13])[C:7]2([CH2:10][CH2:9][CH2:8]2)[CH2:6]1)=[O:4].[Li+].[OH-]>C1COCC1.CO.O>[C:48]([O:47][C:45]([NH:44][CH:39]([C:40]([CH3:43])([CH3:42])[CH3:41])[C:38]([N:15]1[CH2:16][CH:17]([O:19][C:20]2[C:29]3[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=3)[N:23]=[C:22]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH:21]=2)[CH2:18][CH:14]1[C:12]([NH:11][C:5]1([C:3]([OH:4])=[O:2])[C:7]2([CH2:10][CH2:9][CH2:8]2)[CH2:6]1)=[O:13])=[O:52])=[O:46])([CH3:51])([CH3:50])[CH3:49]

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 20769267HCID 20769267, compound

Product 1

HCID 22507515HCID 22507515, compoundYield 93.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 1-{[1-(2-tert-butoxycarbonylamino-3,3-dimethyl-butyryl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-spiro[2.3]-hexane-1-carboxylic acid methyl ester (60 mg, 0.084 mmol) in 3 mL of THF, 1.5 mL of MeOH and 0.4 mL of H2O was added LiOH (30 mg, 1.5 mmol). The mixture was stirred at rt for 3 days. It was then concentrated and partitioned between sat. aq. NaHCO3 and ether. The aqueous layer was acidified to pH=4 with dilute HCl, and extracted three times with EtOAc. The combined EtOAc extracts were dried over magnesium sulfate, filtered and concentrated to provide 55 mg of 1-{[1-(2-tert-butoxycarbonylamino-3,3-dimethyl-butyryl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-spiro[2.3]hexane-1-carboxylic acid as a white solid (93%). LC-MS: (retention time 1.71 min), MS m/z 701 (M++1) (Method D).

Workup

  1. concentrationIt was then concentrated
  2. custompartitioned between sat. aq. NaHCO3 and ether
  3. extractionextracted three times with EtOAc
  4. dry with materialThe combined EtOAc extracts were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-386c73d9c94f4284a44b7d68830b0961
Source dataset
uspto-grants-2005_03
Patent number
US06872805B2

Reaction notes

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