Triethylamine → HCID 178501427, compound

HRID 274775

Reaction equation

HRID 274775 reaction equation
[C:1]([CH2:7][C@@H:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:9]([OH:11])=O)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].Cl.Cl.[CH3:21][O:22][C:23](=[O:32])[C@H:24]([CH2:26][C:27]1[N:31]=[CH:30][NH:29][CH:28]=1)[NH2:25].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[CH3:21][O:22][C:23](=[O:32])[C@H:24]([CH2:26][C:27]1[N:31]=[CH:30][NH:29][CH:28]=1)[NH:25][C:9](=[O:11])[C@@H:8]([CH2:7][C:1](=[O:6])[C:2]([CH3:3])([CH3:4])[CH3:5])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 18611819(R)-alpha-(pivaloylmethyl)hydrocinnamic acidHCID 178419105HCID 178419105, compound

Product 1

HCID 178501427HCID 178501427, compoundYield 81.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 3.0 g (12 mmol) of (R)-α-(pivaloylmethyl)hydrocinnamic acid (see EPA 0.184.550) and 2.66 g (11 mmol) of L-histidine methyl ester dihydrochloride in 340 ml of dimethylformamide is treated at room temperature under a nitrogen atmosphere with 3.45 g (34 mmol) of triethylamine and 4.58 g (12 mmol) of HBTU. The reaction mixture is stirred at room temperature for 5 hours and subsequently evaporated in a high vacuum. The residue is dissolved in 500 ml of ethyl acetate and washed in succession with 100 ml of water, three times with 100 ml of saturated sodium bicarbonate solution each time and 100 ml of saturated sodioum chloride solution. The organic phase is dried over sodium sulphate, evaporated under reduced pressure and the yellowish crude product obtained is chromatographed on silica gel with a 95:5 mixture of methylene chloride and methanol which contains 0.1% ammonia. In this manner there are obtained 3.6 g of N-[(R)-α-(3,3-dimethyl-2-oxobutyl)hydrocinnamoyl]-L-histidine methyl ester as a colourless foam, MS: 399 (M)+.

Workup

  1. customsubsequently evaporated in a high vacuum
  2. dissolutionThe residue is dissolved in 500 ml of ethyl acetate
  3. washwashed in succession with 100 ml of water, three times with 100 ml of saturated sodium bicarbonate solution each time and 100 ml of saturated sodioum chloride solution
  4. dry with materialThe organic phase is dried over sodium sulphate
  5. customevaporated under reduced pressure
  6. customthe yellowish crude product obtained
  7. customis chromatographed on silica gel with a 95:5 mixture of methylene chloride and methanol which

Sources & evidence

ORD record
ord-2d6aa6db6372464ca5b92abd8b7d0faf
Source dataset
uspto-grants-1995_02
Patent number
US05389616

Linked notes

Loading…