2-Bromobenzoic acid → 2-bromo-N-[2-({(1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}amino)-2-oxoethyl]benzamide

HRID 539593Notes

Reaction equation

HRID 539593 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[NH2:39][CH2:40][C:41]([NH:43][C@H:44]([B:49]1[O:53][C@@H:52]2[CH2:54][C@@H:55]3[CH2:58][C@H:57]([C@:51]2([CH3:61])[O:50]1)[C:56]3([CH3:60])[CH3:59])[CH2:45][CH:46]([CH3:48])[CH3:47])=[O:42]>C(Cl)Cl>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:39][CH2:40][C:41]([NH:43][C@H:44]([B:49]1[O:53][C@@H:52]2[CH2:54][C@@H:55]3[CH2:58][C@H:57]([C@:51]2([CH3:61])[O:50]1)[C:56]3([CH3:59])[CH3:60])[CH2:45][CH:46]([CH3:48])[CH3:47])=[O:42])=[O:6]

Participants

7

Reactant 5

HCID 69402-Bromobenzoic acidHCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 533629602-amino-N-{(1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}acetamide

Product 1

HCID 673667952-bromo-N-[2-({(1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}amino)-2-oxoethyl]benzamideYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-bromobenzoic acid (0.124 g, 0.62 mmol) in DCM (2.25 mL) were added EDCI (0.119 g, 0.62 mmol), HOBt (0.084 g, 0.62 mmol), N-methyl morpholine (0.185 mL, 1.68 mmol) and 2-amino-N-{(1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}acetamide (0.2 g, 0.56 mmol). The reaction mixture was allowed to stir for 2 h and was concentrated. The residue was diluted with water and extracted with EtOAc. The organic solutions were combined, washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography to give 2-bromo-N-[2-({(1R)-3-methyl-1-[(3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}amino)-2-oxoethyl]benzamide (0.22 g, 78%).

Workup

  1. concentrationwas concentrated
  2. additionThe residue was diluted with water
  3. extractionextracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-f83c1b8665694b7c9faa3415a60cc9a4
Source dataset
uspto-grants-2014_10
Patent number
US08871745B2

Reaction notes

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