Hydrochloric Acid → (2R,4R)-1-(tert-butoxycarbonyl)-4-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)piperidine-2-carboxylic Acid

HRID 1971300Notes

Reaction equation

HRID 1971300 reaction equation
[Li+].[OH-].[O:3]1[CH2:8][CH2:7][O:6][C:5]2[CH:9]=[C:10]([C:13]([NH:15][C@@H:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@@H:18]([C:29]([O:31]C)=[O:30])[CH2:17]3)=[O:14])[CH:11]=[CH:12][C:4]1=2.Cl>C1COCC1.CO.O>[C:25]([O:24][C:22]([N:19]1[CH2:20][CH2:21][C@@H:16]([NH:15][C:13]([C:10]2[CH:11]=[CH:12][C:4]3[O:3][CH2:8][CH2:7][O:6][C:5]=3[CH:9]=2)=[O:14])[CH2:17][C@@H:18]1[C:29]([OH:31])=[O:30])=[O:23])([CH3:28])([CH3:26])[CH3:27]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 67266415(2R,4R)-1-tert-butyl 2-methyl 4-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)piperidine-1,2-dicarboxylate

Product 1

HCID 67266312(2R,4R)-1-(tert-butoxycarbonyl)-4-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)piperidine-2-carboxylic AcidYield 96.1%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

LiOH (1.23 g, 51.4 mmol) was added to a solution of (2R,4R)-1-tert-butyl 2-methyl 4-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)piperidine-1,2-dicarboxylate (5.4 g, 12.8 mmol) in THF/MeOH/water (3:2:1) (60 mL) and the resulting solution was stirred at room temperature for 18 hours. 1M HCl solution was added to reaction solution to adjust pH to about 3, extracted with ethyl acetate (2×100 mL). The organic layers were dried over MgSO4 and concentrated to give the acid as a white solid 5.0 g (96%). LC-MS: 407.3; 405.3 (t=2.2 min).

Workup

  1. extractionextracted with ethyl acetate (2×100 mL)
  2. dry with materialThe organic layers were dried over MgSO4
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-54462bc9e8e3407c805dfa76bfa0164d
Source dataset
uspto-grants-2013_04
Patent number
US08431597B2

Reaction notes

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