Triethylamine → (2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid ethyl ester

HRID 1469600Notes

Reaction equation

HRID 1469600 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([OH:9])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH2:35]([O:37][C:38](=[O:57])[C@H:39]([CH3:56])[CH2:40][C@H:41]([NH2:55])[CH2:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[CH:45][CH:44]=1)[CH3:36].C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[CH2:35]([O:37][C:38](=[O:57])[C@H:39]([CH3:56])[CH2:40][C@H:41]([NH:55][C:7](=[O:9])[CH2:6][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[CH2:42][C:43]1[CH:44]=[CH:45][C:46]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[CH:47][CH:48]=1)[CH3:36]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 159702-Thiopheneacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 25017086(2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride

Product 1

HCID 67506137(2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of thiophen-2-yl-acetic acid (0.144 mmol) in DMF (5 mL) is added HATU (0.216 mmol). After stirring the mixture at room temperature for 10 minutes, (2R,4S)-4-amino-5-biphenyl-4-yl-2-methyl-pentanoic acid ethyl ester hydrochloride (0.144 mmol) and triethylamine (0.359 mmol) is added and the mixture is stirred at room temperature for 18 hours. The mixture is poured into ethyl acetate and the mixture is washed with aqueous 1M HCl and brine. The organic phase is dried over magnesium sulfate and the solvent is removed under reduced pressure to give (2R,4S)-5-biphenyl-4-yl-2-methyl-4-(2-thiophen-2-yl-acetylamino)-pentanoic acid ethyl ester which is used directly in the subsequent hydrolysis reaction.

Workup

  1. stirringthe mixture is stirred at room temperature for 18 hours
  2. washthe mixture is washed with aqueous 1M HCl and brine
  3. dry with materialThe organic phase is dried over magnesium sulfate
  4. customthe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-eea79c72aa0d4968ad88c3624a1e7ea0
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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