Triethylamine → tert-Butyl N-allyl-N-[2-(methoxy(methyl)amino)-2-oxo-ethyl]carbamate

HRID 521703Notes

Reaction equation

HRID 521703 reaction equation
[CH2:1]([N:4]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][C:6]([OH:8])=O)[CH:2]=[CH2:3].C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.Cl.[CH3:31][NH:32][O:33][CH3:34]>O1CCCC1>[CH2:1]([N:4]([CH2:5][C:6]([N:32]([O:33][CH3:34])[CH3:31])=[O:8])[C:9](=[O:10])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 62493Pivaloyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 10330883Boc-N-(Allyl)-Glycine

Product 1

HCID 86697892tert-Butyl N-allyl-N-[2-(methoxy(methyl)amino)-2-oxo-ethyl]carbamateYield 79.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2-(Allyl(tert-butoxycarbonyl)amino)acetic acid (49.6 g, 156 mmol) is added to tetrahydrofuran (600 mL) at 0° C. followed by the addition of triethylamine (36.3 g, 359 mmol) and pivaloyl chloride (31 g, 353 mmol). The reaction is stirred at room temperature for 3 hours and then cooled to 0° C. N,O-dimethylhydroxylamine hydrochloride (28 g, 283 mmol), triethylamine (33 mL, 237 mmol) and tetrahydrofuran (400 mL) are then added. The ice bath is removed and the reaction stirred at room temperature for 3 hours and concentrated under reduced pressure. The resulting solid is dissolved in water and extracted with ethyl acetate. The organic phases are combined, dried over sodium sulfate, filtered, and the solvent removed under reduced pressure to give a residue. The residue is purified by silica gel column chromatography, eluting with 0-50% gradient of acetone in hexanes to give the title compound (32 g, 54%). 1H NMR (CDCl3) mixture of two rotamers (60:40) δ 1.42, 1.44 (s, 9H), 3.16, 3.17 (s, 3H), 3.66, 3.69 (s, 3H), 3.88-3.98 (m, 2H), 4.01, 4.11 (s, 2H), 5.10-5.18 (m, 2H), 5.73-5.85 (m, 1H).

Workup

  1. temperaturecooled to 0° C
  2. customThe ice bath is removed
  3. stirringthe reaction stirred at room temperature for 3 hours
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe resulting solid is dissolved in water
  6. extractionextracted with ethyl acetate
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customthe solvent removed under reduced pressure
  10. customto give a residue
  11. customThe residue is purified by silica gel column chromatography
  12. washeluting with 0-50% gradient of acetone in hexanes

Sources & evidence

ORD record
ord-7f445ec7d166434f91a3b807c4bd4a2b
Source dataset
uspto-grants-2016_05
Patent number
US09328124B2

Reaction notes

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