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

HRID 82378Notes

Reaction equation

HRID 82378 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)([CH3:16])[C:12]([O:14]C)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].O[Li].O>C1COCC1.O>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)([CH3:16])[C:12]([OH:14])=[O:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 67339056HCID 67339056, compound

Product 1

HCID 673403054-(Tert-butoxycarbonylamino)-2-(4-chlorophenyl)-2-methylbutanoic acidYield 99%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 4-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)-2-methylbutanoate (720 mg, 2.11 mmol) was dissolved in THF (4.2 mL) and water (1.8 mL). The mixture was treated with LiOH—H2O (265 mg, 6.32 mmol) and allowed to stir overnight to completion by LCMS analysis. The mixture was diluted with water and washed twice with diethyl ether (discarded). The aqueous was treated with 3M HCl solution until a pH of about 2 to about 3 (white ppt) and extracted with ethyl acetate several times. The combined organic portions were washed with water, then brine, separated, dried over MgSO4, filtered, and concentrated in vacuo to afford 4-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)-2-methylbutanoic acid as a colorless oil (684 mg, 99%). LCMS (APCI+) [M+H]+326.0; Rt: 2.26 min.

Workup

  1. washwashed twice with diethyl ether (discarded)
  2. additionThe aqueous was treated with 3M HCl solution until a pH of about 2 to about 3 (white ppt)
  3. extractionextracted with ethyl acetate several times
  4. washThe combined organic portions were washed with water
  5. custombrine, separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-049d0f5d4e0643d9880d90294b1165aa
Source dataset
uspto-grants-2014_09
Patent number
US08846681B2

Reaction notes

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