Dimethylcarbamoyl Chloride → HCID 68725513, compound

HRID 2381022Notes

Reaction equation

HRID 2381022 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:8]([OH:20])[CH:7]=1.[CH3:30][N:31]([CH3:35])[C:32](Cl)=[O:33].C(N(CC)CC)C>ClCCl>[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:21][C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:8]([O:20][C:32](=[O:33])[N:31]([CH3:35])[CH3:30])[CH:7]=1

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl Chloride2×HCID 8471Triethylamine2×HCID 10927513HCID 10927513, compound

Product 1

HCID 68725513HCID 68725513, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-3-(4-Benzyloxy-3-hydroxy-phenyl)-2-tert-butoxycarbonylamino-propionic acid methyl ester (401 mg) was dissolved in dichloromethane (8 ml) and N,N-dimethylcarbamoyl chloride (0.092 ml, leg) added. Triethylamine (0.14 ml, 1 eq) was added and the mixture was stirred and heated under reflux. The reaction was monitored by HPLC/MS and further portions of N,N-dimethylcarbamoyl chloride and triethylamine were added in order to complete the reaction. After a total of 8 hours reflux the reaction mixture was evaporated to dryness and absorbed onto silica gel. Chromatography, eluting with mixtures of ethyl acetate-hexane afforded (S)-3-(4-Benzyloxy-3-dimethylcarbamoyloxy-phenyl)-2-tert-butoxycarbonylamino-propionic acid methyl ester as an oil, 315 mg; Rf 0.14 (ethyl acetate-hexane 1:3); HPLC/MS retention time 3.89 min, m/z 473 (MH+). Crystallisation from ethyl acetate-hexane gave (S)-3-(4-benzyloxy-3-dimethylcarbamoyloxy-phenyl)-2-tert-butoxycarbonyl-amino-propionic acid methyl ester as a white solid, 126 mg; NMR (500 MHz, CDCl3) 1.42 (9H, s), 2.95 (3H, s), 2.98-3.04 (5H, m), 3.70 (3H, s), 4.52-4.54 (ca 1H, m), 4.97-5.00 (ca 1H, br d), 5.05 (2H, s), 6.88-6.92 (3H, m), 7.28-7.40 (5H, m).

Workup

  1. temperatureheated
  2. temperatureunder reflux
  3. additionwere added in order
  4. customthe reaction
  5. temperatureAfter a total of 8 hours reflux the reaction mixture
  6. customwas evaporated to dryness
  7. customabsorbed onto silica gel
  8. washChromatography, eluting with mixtures of ethyl acetate-hexane

Sources & evidence

ORD record
ord-08bc46624ecb4913811ce824fbc7d036
Source dataset
uspto-grants-2012_09
Patent number
US08258097B2

Reaction notes

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