Trifluoroacetic acid → 3(R)-amino-N-(l(S)-benzyl-2-hydroxyethyl)succinamic acid benzyl ester trifluoroacetate salt

HRID 613843Notes

Reaction equation

HRID 613843 reaction equation
[CH2:1]([O:8][C:9](=[O:33])[CH2:10][C@@H:11]([NH:25]C(OC(C)(C)C)=O)[C:12]([NH:14][C@@H:15]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:16][OH:17])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37]>C(Cl)Cl>[F:34][C:35]([F:40])([F:39])[C:36]([OH:38])=[O:37].[CH2:1]([O:8][C:9](=[O:33])[CH2:10][C@@H:11]([NH2:25])[C:12]([NH:14][C@@H:15]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:16][OH:17])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 15487943N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(t-butoxycarbonylamino) succinamic acid benzyl ester

Product 1

HCID 701436173(R)-amino-N-(l(S)-benzyl-2-hydroxyethyl)succinamic acid benzyl ester trifluoroacetate salt

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(t-butoxycarbonylamino)succinamic acid benzyl ester (389 mg, 0.851 mmol) in CH2Cl2 (5 mL) was added trifluoroacetic acid (1 mL). After 2.5 h at ambient temperature, the solvent was removed in vacuo to give 3(R)-amino-N-(1(S)-benzyl-2-hydroxyethyl)succinamic acid benzyl ester trifluoroacetate salt as a yellow foam that was placed with 3-(biphenyl-4-yl-)2,5-dimethoxytetrahydrofuran (182 mg, 0.641 mmol) in HOAc (1 mL) and heated to 50° C. After 2 hours, the mixture was allowed to cool, carefully stirred with saturated aqueous NaHCO3 (25 mL), and extracted into CHCl3 (3×15 mL). The combined organic layers were dried over Na2SO4 and evaporated to give a brown oil, 685 mg. Flash column chromatography with 10% MeOH/CH2Cl2 as eluant provided 276 mg (64%) of N-(1(S)-benzyl-2-hydroxyethyl)-3(R)-(3-(biphenyl-4-yl)-1H-pyrrol-1-yl)succinamic acid benzyl ester as a yellow solid. 1H NMR (CDCl3): δ 7.70-7.48 (m, 10H), 7.44 (dd, 2H, J=7.2, 7.8 Hz), 7.38-7.12 (m, 5H), 7.08-6.98 (m, 2H), 6.89 (bm, 1H), 6.63 (dd, 1H, J=2.5, 2.5 Hz), 6.54 (dd, 1H, J=1.2, 1.2 Hz), 5.76 (d, 1H, J=7.5 Hz), 5.10 (dd, 2H, J=12.1, 15.9 Hz), 4.95 (dd, 1H, J=5.0, 8.7 Hz), 4.34-4.00 (bm, 1H), 3.66 (dd, 1H, J=3.7, 11.2 Hz), 3.49 (dd, 1H, J=5.3,11.2 Hz), 3.37 (dd, 1H, J=5.0, 16.8 Hz), 3.18 (dd, 1H, J=8.7, 16.8 Hz), 2.74 (ddd, 2H, J=6.5, 13.7, 15.9 Hz). IR (KBr): 3314, 3029, 2925, 1731, 1658, 1548, 1495, 1355, 1196, 1165, 761, 698 cm-1 ; Anal. calculated for C36H34N2O4.0.5H2O: C, 76.17; H, 6.22; N, 4.94. Found C, 76.24; H, 6.18; N, 4.97.

Workup

  1. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-69a03d18086b415e88df4a6a4ce16821
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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