Aminoisobutyric acid → Ammonium Hydroxide

HRID 1890717Notes

Reaction equation

HRID 1890717 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:12])[CH:10]=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:21][C:22]([C:25]([OH:27])=[O:26])([CH3:24])[NH2:23].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CC(O)=O.O>[NH4+:13].[OH-:11].[C:16]([O:15][C:14]([NH:13][C:9]([C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=1)([CH3:12])[CH2:10][NH:23][C:22]([CH3:24])([C:25]([OH:27])=[O:26])[CH3:21])=[O:20])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 3

HCID 6119Aminoisobutyric acidHCID 5049666Sodium triacetoxyborohydride2×HCID 86616399tert-butyl N-[2-(3,5-difluorophenyl)-1-oxopropan-2-yl]carbamate

Product 2

HCID 14923Ammonium HydroxideHCID 68747550HCID 68747550, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a stirred solution of (±)-tert-butyl [1-(3,5-difluorophenyl)-1-methyl-2-oxoethyl]carbamate (4.00 g, 14.0 mmol, described in U.S. Patent Application Publication No. US 2007/0265225) and 2-methylalanine (4.34 g, 42.1 mmol) in AcOH (25 mL) was added sodium triacetoxyborohydride (3.57 g, 16.8 mmol). The reaction mixture was stirred for 24 h, with additional sodium triacetoxyborohydride (1.00 g) added at 16 and 20 h. The reaction mixture was diluted with water (75 mL) and extracted with CH2Cl2 (4×50 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—97:3:1 to 85:15:1, to give the title compound. MS: m/z=373 (M+1).

Workup

  1. additionadded at 16 and 20 h
  2. extractionextracted with CH2Cl2 (4×50 mL)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel chromatography
  7. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-50a77b5992ab4a1d8f307428a2d7a1f7
Source dataset
uspto-grants-2013_08
Patent number
US08507477B2

Reaction notes

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