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

HRID 881832Notes

Reaction equation

HRID 881832 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 hydrochloride2×

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 (intermediate 29: 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-f760c250af9d427b8bc52c67f0f06785
Source dataset
uspto-grants-2015_03
Patent number
US08993631B2

Reaction notes

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