Triethylamine → tert-Butyl (2-(methoxy(methyl)amino)-2-oxoethyl)carbamate

HRID 1500228Notes

Reaction equation

HRID 1500228 reaction equation
[NH:1]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:2][C:3]([OH:5])=O.Cl.[CH3:14][NH:15][O:16][CH3:17].C(N(CC)CC)C.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.ClCCl>[CH3:17][O:16][N:15]([CH3:14])[C:3](=[O:5])[CH2:2][NH:1][C:6](=[O:7])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 78288N-(tert-butoxycarbonyl)glycineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 4428209tert-Butyl (2-(methoxy(methyl)amino)-2-oxoethyl)carbamateYield 94.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of Boc-Gly-OH (4250 g, 24.26 mol), N,O-dimethylhydroxylamine-HCl (2839 g, 29.10 mol) and DMAP (297 g, 2.43 mol) in dichloromethane (36 L), is added triethylamine (5.54 L) at 0° C. over a period of 90 min followed by the addition of EDC hydrochloride (5674 g, 29.60 mol). The mixture is stirred at 0° C. for 1 h then warmed to room temp for 24 h. The reaction mixture is cooled to 0° C. and quenched with 1.0M HCl to pH 3 to 4, stirred at room temp for 20 min, then allowed to stand and separate. The organic phase is washed successively with 1.0M HCl (15 L), water (15.0 L) and brine (8.0 L), dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure to provide the title compound (4985 g; 94% yield) as a white solid.

Workup

  1. temperaturethen warmed to room temp for 24 h
  2. temperatureThe reaction mixture is cooled to 0° C.
  3. customquenched with 1.0M HCl to pH 3 to 4
  4. stirringstirred at room temp for 20 min
  5. customseparate
  6. washThe organic phase is washed successively with 1.0M HCl (15 L), water (15.0 L) and brine (8.0 L)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated under reduced pressure

Sources & evidence

ORD record
ord-3f630f58d7f04d5190ac8b4a42984c42
Source dataset
uspto-grants-2015_12
Patent number
US09206139B2

Reaction notes

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