Lithium hydroxide, monohydrate → 4-(Tert-butoxycarbonylamino)-2-(4-chlorophenyl)-4-methylpentanoic acid

HRID 79544Notes

Reaction equation

HRID 79544 reaction equation
[OH2:1].[OH-].[Li+].[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[C:15](=[O:16])[N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:13]([CH3:25])([CH3:24])[CH2:12]2)=[CH:7][CH:6]=1>C1COCC1.CO.O>[C:20]([O:19][C:17]([NH:14][C:13]([CH3:25])([CH3:24])[CH2:12][CH:11]([C:8]1[CH:9]=[CH:10][C:5]([Cl:4])=[CH:6][CH:7]=1)[C:15]([OH:1])=[O:16])=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66617851Tert-butyl 4-(4-chlorophenyl)-2,2-dimethyl-5-oxopyrrolidine-1-carboxylate

Product 1

HCID 666178284-(Tert-butoxycarbonylamino)-2-(4-chlorophenyl)-4-methylpentanoic acidYield 63.2%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

Lithium hydroxide hydrate (6.44 mL, 232 mmol) was added to a stirred solution of tert-butyl 4-(4-chlorophenyl)-2,2-dimethyl-5-oxopyrrolidine-1-carboxylate (7.5 g, 23.2 mmol) in THF/MeOH/H2O (30 mL/30 mL/30 mL) at room temperature. The mixture was stirred at room temperature overnight and concentrated in vacuo. The mixture was taken up into water (200 mL), washed with EtOAc (100 mL), acidified with concentrated HCl and extracted into EtOAc (2×200 mL). The mixture was dried over Na2SO4 and concentrated in vacuo. Residual HCl was removed by evaporating from toluene to give 4-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)-4-methylpentanoic acid (5.0 g, 63.2% yield) as a solid. LCMS (APCI+) [M-Boc+H]+ 242.0; Rt: 2.8 min.

Workup

  1. concentrationconcentrated in vacuo
  2. washwashed with EtOAc (100 mL)
  3. extractionextracted into EtOAc (2×200 mL)
  4. dry with materialThe mixture was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customResidual HCl was removed
  7. customby evaporating from toluene

Sources & evidence

ORD record
ord-fc0c78d274b846478a14e7f8c09b2079
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

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