Lithium Hydroxide → HCID 11992410, compound

HRID 553068Notes

Reaction equation

HRID 553068 reaction equation
C[O:2][C:3](=[O:39])[C@H:4]([CH2:29][C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[NH:32][CH:31]=1)[NH:5][C:6](=[O:28])[CH2:7][CH2:8][C:9](=[O:27])[C@@H:10]([NH:18][C:19](=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1COCC1.CO.[Li+].[OH-]>C(O)(=O)C>[C:19]([NH:18][C@@H:10]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:9](=[O:27])[CH2:8][CH2:7][C:6]([NH:5][C@H:4]([C:3]([OH:39])=[O:2])[CH2:29][C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[NH:32][CH:31]=1)=[O:28])(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 21899815MeOH tetrahydrofuranHCID 67163963(5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-tryptophan methyl ester

Product 1

HCID 11992410HCID 11992410, compoundYield 95.9%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of the compound (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-tryptophan methyl ester (170 mg, 0.3222 mmol, 1.0 eq.) in a mixture THF-MeOH (ratio 3:2) (10 mL) was added 0.5N LiOH (5.0 mL). The resulting yellowish mixture was stirred at room temperature for 30 min during which TLC shows the complete disappearance of the starting material. The reaction mixture was then neutralized with glacial acetic acid and the extracted with EtOAc (3×25 mL), dried over anhydrous MgSO4 and evaporation of the solvent gave a crude residue, which was subjected to column chromatography on silica gel elution with 30% MeOH-EtOAc afforded the free acid (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-tryptophan 5b as a pale yellow solid (0.158 g, 95%); mp 171-173° C.; Rf 0.38 (30% MeOH-EtOAc); IR (KBr) ν 1720 (CO), 3250 (broad, COOH) cm−1; 1H NMR (400 MHz, CDCl3) δH 2.31 (2H, m, —CH2CO), 2.70 (2H, m, —CH2CO), 2.96 (1H, m, —CHαPh), 3.24 (3H, m, —CHβPh and —CH2Trp),), 4.84 (1H, m, —CH—), 4.90 (1H, m, —CH—), 6.49 (1H, t, J=7.2 Hz, —NH), 6.92-7.66 (16H, m, Ar—H and —NH) and 8.48 (1H, d, J=6.0 Hz, —NH); 13C NMR (100 MHz, CDCl3) δC 27.2, 29.5, 35.0, 35.1, 36.5, 53.2, 59.5, 59.6, 109.5, 111.4, 118.5, 119.6, 122.0, 123.5, 127.0, 127.1 (2C), 127.4, 128.6, 128.7 (2C), 129.2, 132.0, 133.5, 136.1, 167.7, 172.4, 174.6 and 207.8; HRMS m/z calcd for C30H29N3O5 (M+) 511.21072, found 511.21072. [± The carboxylic acid and amide protons were not observed, presumably, due to rapid exchange with water in the deuteriated NMR solvent.]

Workup

  1. extractionthe extracted with EtOAc (3×25 mL)
  2. dry with materialdried over anhydrous MgSO4 and evaporation of the solvent
  3. customgave a crude residue, which
  4. washwas subjected to column chromatography on silica gel elution with 30% MeOH-EtOAc

Sources & evidence

ORD record
ord-671f1dba43ed47ad93706777fa9030de
Source dataset
uspto-grants-2011_05
Patent number
US07951834B2

Reaction notes

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