4-Bromoaniline → 1-Methylethyl{(3S)-3-[(4-bromophenyl)amino]butanoyl}carbamate

HRID 2366846Notes

Reaction equation

HRID 2366846 reaction equation
[C:1]([NH:6][C:7](=[O:12])[O:8][CH:9]([CH3:11])[CH3:10])(=[O:5])/[CH:2]=[CH:3]/[CH3:4].[Br:13][C:14]1[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=1>C1(C)C=CC=CC=1>[Br:13][C:14]1[CH:20]=[CH:19][C:17]([NH:18][C@@H:3]([CH3:4])[CH2:2][C:1]([NH:6][C:7](=[O:12])[O:8][CH:9]([CH3:11])[CH3:10])=[O:5])=[CH:16][CH:15]=1

Participants

4

Reactant 2

HCID 78074-BromoanilineHCID 866691361-methylethyl (2E)-2-butenoylcarbamate2×

Product 1

HCID 681848681-Methylethyl{(3S)-3-[(4-bromophenyl)amino]butanoyl}carbamate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Similarly a second batch of 1-methylethyl (2E)-2-butenoylcarbamate (Intermediate 49, 8.51 g, 49.7 mmol) was stirred in Toluene (255 ml) under nitrogen and (R-BINAP)ditriflatebis(acetonitrile)palladium(II) (3.04 g, 2.73 mmol) added. The catalyst formed a gummy ball, the solution turned to an opaque yellow mixture and was stirred for 20 mins. 4-bromoaniline (12.83 g, 74.6 mmol) was added, the solution turned a clear light brown and the gummy catalyst dissolved further. The mixture was stirred overnight. The two reaction mixtures were combined and loaded on to a 1.5 kg Isco silica Redisep column. The column was eluted with DCM:MeOH (0%−>0.5%, 19 CV). The clean, product containing fractions were evaporated to a pale brown oil. The mixture was dried in a vacuum oven overnight at 40° C. to give a white solid (24.2 g, 67% overall).

Workup

  1. customThe catalyst formed a gummy ball
  2. dissolutiondissolved further
  3. stirringThe mixture was stirred overnight
  4. customThe two reaction mixtures
  5. washThe column was eluted with DCM
  6. additionThe clean, product containing fractions
  7. customwere evaporated to a pale brown oil
  8. customThe mixture was dried in a vacuum oven overnight at 40° C.
  9. customto give a white solid (24.2 g, 67% overall)

Sources & evidence

ORD record
ord-1f264cb45c414f90b81ec3233308d136
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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