Potassium Carbonate → Carbamic acid, N-[(1S)-1-[[(3-hydroxy-2,2-dimethylpropyl)amino]carbonyl]-2-methylpropyl]-, 1,1-dimethylethyl ester

HRID 2170265Notes

Reaction equation

HRID 2170265 reaction equation
[NH2:1][CH2:2][C:3]([CH3:7])([CH3:6])[CH2:4][OH:5].[CH3:8][C:9]([CH3:29])([O:11][C:12]([NH:14][C@@H:15]([C:19](ON1C(=O)CCC1=O)=[O:20])[CH:16]([CH3:18])[CH3:17])=[O:13])[CH3:10].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[OH:5][CH2:4][C:3]([CH3:7])([CH3:6])[CH2:2][NH:1][C:19]([C@@H:15]([NH:14][C:12](=[O:13])[O:11][C:9]([CH3:8])([CH3:29])[CH3:10])[CH:16]([CH3:18])[CH3:17])=[O:20]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1173261-Propanol, 3-amino-2,2-dimethyl-HCID 57563838HCID 57563838, compound

Product 1

HCID 86669326Carbamic acid, N-[(1S)-1-[[(3-hydroxy-2,2-dimethylpropyl)amino]carbonyl]-2-methylpropyl]-, 1,1-dimethylethyl esterYield 88%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of commercial 3-amino-2,2-dimethyl-1-propanol (1.7 g, 16.5 mmol), N-[(1,1-dimethylethoxy)carbonyl]-D-Valine, 2,5-dioxo-1-pyrrolidinyl ester (Giuntini F. et al., J. Med. Chem. (2009), 52(13), 4026-4037, incorporated herein by reference) (4.7 g, 15.0 mmol) and 1M aqueous potassium carbonate (10 mL, 10.0 mmol) in acetonitrile (30 mL) was stirred at room temperature for 2 h. The mixture was concentrated to about one third of its volume, diluted with 1M hydrochloric acid and extracted three times with ethyl acetate. The combined organic layers were washed with water, dried over magnesium sulfate, filtered and the filtrate evaporated to a residue. The crude product was purified by silica gel chromatography using hexane/ethyl acetate (50:50) to isolate 4 g (88% yield) of tert-butyl N-[(1S)-1-[(3-hydroxy-2,2-dimethyl-propyl)carbamoyl]-2-methyl-propyl]carbamate.

Workup

  1. concentrationThe mixture was concentrated to about one third of its volume
  2. additiondiluted with 1M hydrochloric acid
  3. extractionextracted three times with ethyl acetate
  4. washThe combined organic layers were washed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customthe filtrate evaporated to a residue
  8. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-95a0ec89dd5443ce9913c745d7a13424
Source dataset
uspto-grants-2015_06
Patent number
US09051248B2

Reaction notes

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