Lithium hydroxide, monohydrate → (R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acid

HRID 2061007Notes

Reaction equation

HRID 2061007 reaction equation
C[O:2][C:3](=[O:24])[CH2:4][C@H:5]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([F:14])=[CH:9][C:8]=1[F:15].O[Li].O.C([O-])(O)=O.[Na+]>C1COCC1.O>[C:20]([O:19][C:17]([NH:16][C@H:5]([CH2:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([F:14])=[CH:9][C:8]=1[F:15])[CH2:4][C:3]([OH:24])=[O:2])=[O:18])([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 516892Sodium BicarbonateHCID 11359981Benzenebutanoicacid,b-[[(1,1-diMethylethoxy)carbonyl]aMino]-2,4,5-trifluoro-,Methylester,(bR)-

Product 1

HCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acidYield 95.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-Methyl-3-[N-(tert-butoxycarbonyl)amino]-4-(2,4,5-tri-fluorophenyl)butanoate of Example 4 (1.28 g, 3.69 mmol) in 15 mL THF and 15 mL water was added 3 equiv. LiOH.H2O. The reaction mixture was stirred for 16 h. 10 ml saturated NaHCO3 was added. THF was evaporated and the aq solution was acidified to pH 2-3 with NaHSO4, then extracted by ethyl acetate (3×15 mL). The combined organic phase was washed with brine and dried over Na2SO4. Concentration in vacuo afforded 1.17 g of white solid (95.1%). 1H NMR (300 MHz, CD3OD) 7.13-7.03 (m, 2H), 4.20-4.10 (m, 1H), 3.00-2.90 (m, 1H), 2.75-2.60 (m, 1H), 2.45-2.55 (m, 2H), 1.35 (s, 9H)

Workup

  1. customTHF was evaporated
  2. extractionextracted by ethyl acetate (3×15 mL)
  3. washThe combined organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-35bd1d69853e447eb6d2ad7b2f54ff28
Source dataset
uspto-grants-2012_10
Patent number
US08278486B2

Reaction notes

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