Hydrochloric Acid → (R)-2-((tert-Butoxycarbonyl)amino)-4,4-dimethylpentanoic acid

HRID 2237368Notes

Reaction equation

HRID 2237368 reaction equation
C[O:2][C:3](=[O:18])[C@@H:4]([CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].O.[OH-].[Li+].Cl.[Cl-].[Na+]>O1CCCC1.O>[C:9]([O:8][C:6]([NH:5][C@@H:4]([C:3]([OH:18])=[O:2])[CH2:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:7])([CH3:12])([CH3:10])[CH3:11]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 168937Lithium hydroxide, monohydrateHCID 59302429N-tert-Butoxycarbonyl-3-tert-butyl-D-alanine methyl ester

Product 1

HCID 7021114(R)-2-((tert-Butoxycarbonyl)amino)-4,4-dimethylpentanoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-tert-Butoxycarbonyl-3-tert-butyl-D-alanine methyl ester (Example 5A, 60 g, 231 mmol) is dissolved in tetrahydrofuran p.a. (463 ml). At RT, a solution of lithium hydroxide monohydrate (19.4 g, 462.7 mmol) in water (463 ml) is slowly added dropwise. When the HPLC chromatogram (Method 2) shows complete conversion (about 20 h), the reaction mixture is cautiously adjusted to pH 3-4 with 1 N aqueous hydrochloric acid with ice cooling. Sodium chloride (150 g) is added to the reaction mixture in order subsequently to extract it with ethyl acetate (2×500 ml). The combined organic phases are dried with a saturated sodium chloride solution and then with sodium sulfate and filtered. The filtrate is concentrated on a rotary evaporator and dried under high vacuum. 55.4 g (98% of theory) of the title compound are obtained.

Workup

  1. customconversion (about 20 h)
  2. extractionto extract it with ethyl acetate (2×500 ml)
  3. dry with materialThe combined organic phases are dried with a saturated sodium chloride solution
  4. filtrationwith sodium sulfate and filtered
  5. concentrationThe filtrate is concentrated on a rotary evaporator
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-f4efd37cc68f4de69403269579c244a3
Source dataset
uspto-grants-2010_05
Patent number
US07718611B2

Reaction notes

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