Dicyclohexylcarbodiimide → Methyl 2-(3-(4-((R)-2-hydroxy-2-phenylacetamido)phenyl) isoxazole-5-carboxamido)-3-methylbutanoate

HRID 75853Notes

Reaction equation

HRID 75853 reaction equation
[OH:1][C@H:2]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3]([OH:5])=O.[NH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:23]=[C:22]([C:24]([NH:26][CH:27]([CH:32]([CH3:34])[CH3:33])[C:28]([O:30][CH3:31])=[O:29])=[O:25])[O:21][N:20]=2)=[CH:15][CH:14]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1>>[OH:1][C@H:2]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:23]=[C:22]([C:24]([NH:26][CH:27]([CH:32]([CH3:34])[CH3:33])[C:28]([O:30][CH3:31])=[O:29])=[O:25])[O:21][N:20]=2)=[CH:15][CH:14]=1)=[O:5]

Participants

5

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 11914(-)-Mandelic acidHCID 757711-HydroxybenzotriazoleHCID 67352790Methyl 2-(3-(4-aminophenyl)isoxazole-5-carboxamido)-3-methylbutanoate

Product 1

HCID 67353472Methyl 2-(3-(4-((R)-2-hydroxy-2-phenylacetamido)phenyl) isoxazole-5-carboxamido)-3-methylbutanoateYield 39.6%

Procedure

To (R)-2-hydroxy-2-phenylacetic acid (200 mg), methyl 2-(3-(4-aminophenyl) isoxazole-5-carboxamido)-3-methylbutanoate (417 mg), in N,N′-Dimethyl formamide (5 ml), DCC (406 mg) and HOBT (177 mg) were added and stirred at RT for 16 hours. The reaction mixture was filtered and concentrated to obtain brown oil which was purified by column chromatography (silica gel, EtOAc—CHCl3) to obtain pale brown solid which was crystallized from DCM-Petroleum ether to yield 235 mg (39%) of the title compound as off white solid. MS (ES+): m/z 452 (M+1); 1H NMR (DMSO-d6; 300 MHz): δ 10.19 (s, 1H), 9.2 (d, 1H), 7.88 (d, 4H), 7.69 (s, 1H), 7.54 (m, 2H), 7.39-7.27 (m, 3H), 6.51 (d, 1H), 5.13 (d, 1H), 4.3 (m, 1H), 3.67 (s, 3H), 2.24 (m, 1H), 0.96 (d, 6H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated
  3. customto obtain brown oil which
  4. customwas purified by column chromatography (silica gel, EtOAc—CHCl3)
  5. customto obtain pale brown solid which
  6. customwas crystallized from DCM-Petroleum ether

Sources & evidence

ORD record
ord-3bdc70ef764a44cd916f066b9e0c2012
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Reaction notes

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