Trifluoroacetic acid → 3(R)-[3-(biphenyl-4-yl)-1H-pyrrol-1-yl]-N-[2-hydroxy-1(S)-(hydroxymethyl)-2-methylpropyl]succinamic acid benzyl ester

HRID 613855Notes

Reaction equation

HRID 613855 reaction equation
[CH2:1]([O:8][C:9](=[O:30])[CH2:10][C@@H:11]([NH:22][C:23](OC(C)(C)C)=O)[C:12]([NH:14][C@@H:15]([CH2:20][OH:21])[C:16]([OH:19])([CH3:18])[CH3:17])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[C:38]1([C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)[CH:43]=[CH:42][C:41]([CH:44]2[CH2:48]C(OC)O[CH:45]2OC)=[CH:40][CH:39]=1>ClCCCl>[CH2:1]([O:8][C:9](=[O:30])[CH2:10][C@@H:11]([N:22]1[CH:23]=[CH:45][C:44]([C:41]2[CH:42]=[CH:43][C:38]([C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)=[CH:39][CH:40]=2)=[CH:48]1)[C:12]([NH:14][C@@H:15]([CH2:20][OH:21])[C:16]([OH:19])([CH3:17])[CH3:18])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 183803263-Biphenyl-4-yl-2,5-dimethoxytetrahydrofuranHCID 538878773(R)-t-butoxycarbonylamino-N-(2hydroxy-1-(S)-hydroxymethyl-2-methylpropyl)succinamic acid benzyl ester

Product 1

HCID 701429583(R)-[3-(biphenyl-4-yl)-1H-pyrrol-1-yl]-N-[2-hydroxy-1(S)-(hydroxymethyl)-2-methylpropyl]succinamic acid benzyl esterYield 11%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

According to the procedure described in Example 1(c) for N-(8-oxo-4-oxa-1,7-diazatricyclo-[9.6.1.012,17 ]-octa-deca-11(18),12,14,16-tetraen-9S-yl)-3(R)-(3-phenyl-1H-pyrrol-1-yl)succinamic acid benzyl ester, 3(R)-t-butoxycarbonylamino-N-(2-hydroxy-1(S)-hydroxymethyl-2-methyl-propyl)succinamic acid benzyl ester was deprotected with trifluoroacetic acid. The crude amine salt and 3-biphenyl-4-yl-2,5-dimethoxy-tetrahydrofuran (prepared as described in Example 1(a)) were condensed in anhydrous 1,2-dichloroethane with trifluoroacetic acid to give in 11% yield 3(R)-[3-(biphenyl4-yl)-1H-pyrrol-1-yl]-N-[2-hydroxy-1(S)-(hydroxymethyl)-2-methylpropyl]succinamic acid benzyl ester as an amorphous solid. 1H NMR (acetone-d6): δ 7.67-7.61 (m, 6H), 7.48 (t, 2H, J=7.7 Hz), 7.39 (t, 1H, J=1.8 Hz), 7.37-7.27 (m, 6H), 7.09 (bd, 1H, J=9.2 Hz), 6.96 (t, 1H, J=2.6 Hz), 6.53 (dd, 1H, J=1.7, 2.8 Hz), 5.35 (t, 1H, J=7.4 Hz), 5.11 (s, 2H), 3.81-3.62 (m, 3H), 3.39 (dd, 1H, J=6.8, 16.4 Hz), 3.12 (dd, 1H, J=7.7, 16.6 Hz), 1.24 (s, 3H), 1.21 (s, 3H). Anal. Calculated for C32H34N2O5 : C, 72.98; H, 6.51; N, 5.32. Found: C, 72.83; H, 6.60; N, 5.24.

Sources & evidence

ORD record
ord-3ac532378fbe401fa0bca5d66a5bec4a
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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