1,2-Dichloroethane → Benzyl (3-{2-[methoxy(methyl)amino]-2-oxoethyl}phenyl)carbamate

HRID 243644Notes

Reaction equation

HRID 243644 reaction equation
C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:19][NH:20][O:21][CH3:22].C(Cl)CCl.[CH2:27]([O:34][C:35]([NH:37][C:38]1[CH:39]=[C:40]([CH2:44][C:45]([OH:47])=O)[CH:41]=[CH:42][CH:43]=1)=[O:36])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[CH3:22][O:21][N:20]([CH3:19])[C:45](=[O:47])[CH2:44][C:40]1[CH:39]=[C:38]([NH:37][C:35](=[O:36])[O:34][CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:43]=[CH:42][CH:41]=1

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 57907509HCID 57907509, compound2×

Product 1

HCID 57907449Benzyl (3-{2-[methoxy(methyl)amino]-2-oxoethyl}phenyl)carbamateYield 74%

Procedure

To a suspension of 24.7 g (87 mmol) of (3-{[(benzyloxy)carbonyl]amino}phenyl)acetic acid in 200 mL of dichloromethane (from Step B) was added triethylamine (30.2 mL, 173 mmol) which resulted in some exotherming (+5° C.) and the suspension becoming a solution. After 10 min cooling, HOBt (13.2 g, 87 mmol), N,O-dimethylhydroxylamine HCl (8.5 g, 87 mmol) was added to the solution followed by EDC (16.6 g, 87 mmol) and the resulting mixture stirred at room temperature overnight under nitrogen atmosphere. The solution was transferred to a separatory funnel and washed with 1 M HCl which caused an emulsion. Methanol was added to break up the emulsion and the aqueous was partitioned off. The organics were dried over sodium sulfate, filtered and concentrated under vacuum. Recrystallization of the residue from 1000 mL of 70% hexane in ethyl acetate (heated to reflux and then cooled to room temperature overnight) afforded the title compound (21 g, 74%) as a white solid. LC-MS: m/z (ES) 329 (MH)+.

Workup

  1. customresulted in some exotherming (+5° C.)
  2. temperatureAfter 10 min cooling
  3. customThe solution was transferred to a separatory funnel
  4. washwashed with 1 M HCl which
  5. additionMethanol was added
  6. customthe aqueous was partitioned off
  7. dry with materialThe organics were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customRecrystallization of the residue from 1000 mL of 70% hexane in ethyl acetate (
  11. temperatureheated
  12. temperatureto reflux
  13. temperaturecooled to room temperature overnight)

Sources & evidence

ORD record
ord-0fa17e88f14942bb999764441cba794e
Source dataset
uspto-grants-2014_02
Patent number
US08653260B2

Reaction notes

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