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

HRID 1685460Notes

Reaction equation

HRID 1685460 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-5cd0ed72c7ad4aa7b02215916f7ce6f2
Source dataset
uspto-grants-2012_04
Patent number
US08148401B2

Reaction notes

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