Lithium Hydroxide → HCID 11992491, compound

HRID 553069Notes

Reaction equation

HRID 553069 reaction equation
C(N[C@@H](CC1C=CC=CC=1)C(=O)CCC(N[C@H](C(O)=O)CC1C2C(=CC=CC=2)NC=1)=O)(=O)C1C=CC=CC=1.C[O:40][C:41](=[O:74])[C@H:42]([CH2:67][C:68]1[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=1)[NH:43][C:44](=[O:66])[CH2:45][CH2:46][C:47](=[O:65])[C@@H:48]([NH:56][C:57](=[O:64])[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)[CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.[Li+].[OH-]>C1COCC1.CO>[C:57]([NH:56][C@@H:48]([CH2:49][C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1)[C:47](=[O:65])[CH2:46][CH2:45][C:44]([NH:43][C@H:42]([C:41]([OH:74])=[O:40])[CH2:67][C:68]1[CH:69]=[CH:70][CH:71]=[CH:72][CH:73]=1)=[O:66])(=[O:64])[C:58]1[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=1

Participants

5

Reactant 3

HCID 3939Lithium Hydroxide2×HCID 11992410HCID 11992410, compoundHCID 57956921HCID 57956921, compound

Product 1

HCID 11992491HCID 11992491, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

The experimental procedure employed for the synthesis of compound 5b was followed using the (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-phenylalanine methyl ester (200 mg, 0.4094 mmol, 1.0 eq.), 0.5N LiOH (5.0 mL) and a mixture THF-MeOH (ratio 3:2) (10 mL) was added 0.5N LiOH (5.0 mL). Work-up and column chromatography on silica gel elution with 20% MeOH-EtOAc afforded the free acid (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-phenylalanine 5c as a yellow oil (0.187 g, 97%); IR (liquid film) ν 1720 (CO), 3100 (broad, COOH) cm−1; 1H NMR (300 MHz, CDCl3) δH 2.46 (2H, m, —CH2CO), 2.80 (2H, m, —CH2CO), 3.00-3.31 (4H, m, 2×—CH2Ph), 4.81 (1H, q, J=6.0 Hz), 4.98 (1H, ddd, J=2.5, 7.0 and 9.0 Hz, —CH—), 6.30 (1H, m, —NH), 6.94 (1H, t, J=9.3 Hz, Ar—H) and 7.10-7.74 (16H, m, Ar—H and —NH); 13C NMR (75 MHz, CDCl3) δC 29.1, 29.7, 35.3, 36.8, 37.3, 53.3, 59.5, 59.6, 67.7, 127.1 (2C), 127.2 (2C), 128.5, 128.6, 128.7, 129.2, 129.3, 129.4, 131.9, 133.5, 135.8, 136.1, 167.5, 172.0, 174.9 and 207.7; HRMS m/z calcd for C28H28N2O5 (M+) 472.19982, found 472.19982. [± The carboxylic acid and amide protons were not observed, presumably, due to rapid exchange with water in the deuteriated NMR solvent.]

Workup

  1. washcolumn chromatography on silica gel elution with 20% MeOH-EtOAc

Sources & evidence

ORD record
ord-bbaefd3f29c844b69c228f6786f3683a
Source dataset
uspto-grants-2011_05
Patent number
US07951834B2

Reaction notes

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