Water → (S)-3-tert-Butoxycarbonylamino-2-p-tolyl-propionic acid

HRID 1192338Notes

Reaction equation

HRID 1192338 reaction equation
C[O:2][C:3](=[O:21])[CH:4]([C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1)[CH2:5][NH:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].O.O.[OH-].[Li+]>C1COCC1>[C:10]([O:9][C:7]([NH:6][CH2:5][CH:4]([C:14]1[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=1)[C:3]([OH:21])=[O:2])=[O:8])([CH3:13])([CH3:12])[CH3:11]

Participants

5

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 675386203-Tert-butoxycarbonylamino-2-p-tolyl-propionic acid methyl ester

Product 1

HCID 67539562(S)-3-tert-Butoxycarbonylamino-2-p-tolyl-propionic acidYield 93.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The 3-tert-butoxycarbonylamino-2-p-tolyl-propionic acid methyl ester (12.3 g, 41.9 mmol) was dissolved in 200 mL 1:1 THF:water and treated with lithium hydroxide monohydrate (2.64 g, 62.9 mmol) at room temperature. The reaction was stirred at room temperature overnight to completion and concentrated in vacuo. The oily mixture was partitioned with water and washed with EtOAc (discarded). The aqueous was treated with solid KHSO4 until pH<2, then extracted with EtOAc. The combined organic was dried over Na2SO4, filtered, and concentrated in vacuo to afford the 3-tert-butoxycarbonylamino-2-p-tolyl-propionic acid as a white solid (10.95 g, 93%). 1H NMR (ca. 1:1 mixture of rotamers) (CDCl3, 400 MHz) δ 10.40-8.40 (br s, 1H), 7.16 (d, J=8.4 Hz, 2H), 7.13 (d, J=8.4 Hz, 2H), 6.80 or 4.91 (br s, 1H), 3.86 and 3.75 (m, 1H), 3.55 (m, 1H), 3.47 (m, 2H), 2.31 (s, 3H), 1.44 and 1.41 (s, 9H). LCMS (APCI−) m/z 557 [2M−H]−. HPLC R2=2.80 min.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe oily mixture was partitioned with water
  3. washwashed with EtOAc (discarded)
  4. additionThe aqueous was treated with solid KHSO4 until pH<2
  5. extractionextracted with EtOAc
  6. dry with materialThe combined organic was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-945a9642d9fa4b4ca221a8c935fee4b1
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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