Lithium hydroxide, monohydrate → 4-{(S)-5-(6-Bromo-2-methoxy-naphthalen-1-ylmethyl)-3-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carbonyl}-benzoic acid

HRID 1481909Notes

Reaction equation

HRID 1481909 reaction equation
C[O:2][C:3](=[O:52])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([N:12]2[CH2:18][C@H:17]([NH:19][C:20](=[O:32])[C@@H:21]([N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH3:24])[CH3:22])[C:16](=[O:33])[N:15]([CH2:34][C:35]3[C:44]4[C:39](=[CH:40][C:41]([Br:45])=[CH:42][CH:43]=4)[CH:38]=[CH:37][C:36]=3[O:46][CH3:47])[C:14]3[CH:48]=[CH:49][CH:50]=[CH:51][C:13]2=3)=[O:11])=[CH:6][CH:5]=1.O[Li].O>C1COCC1.CO.O.O>[Br:45][C:41]1[CH:40]=[C:39]2[C:44](=[CH:43][CH:42]=1)[C:35]([CH2:34][N:15]1[C:16](=[O:33])[C@@H:17]([NH:19][C:20](=[O:32])[C@@H:21]([N:23]([C:25]([O:27][C:28]([CH3:30])([CH3:31])[CH3:29])=[O:26])[CH3:24])[CH3:22])[CH2:18][N:12]([C:10]([C:7]3[CH:8]=[CH:9][C:4]([C:3]([OH:52])=[O:2])=[CH:5][CH:6]=3)=[O:11])[C:13]3[CH:51]=[CH:50][CH:49]=[CH:48][C:14]1=3)=[C:36]([O:46][CH3:47])[CH:37]=[CH:38]2

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 902212384-{(S)-5-(6-Bromo-2-methoxy-naphthalen-1-ylmethyl)-3-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carbonyl}-benzoic acid methyl ester2×

Product 1

HCID 902209134-{(S)-5-(6-Bromo-2-methoxy-naphthalen-1-ylmethyl)-3-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carbonyl}-benzoic acidYield 91.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a solution of 4-{(S)-5-(6-bromo-2-methoxy-naphthalen-1-ylmethyl)-3-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-4-oxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepine-1-carbonyl}-benzoic acid methyl ester (Intermediate 19) (4 g, 5.175 mmol) in THF-MeOH-water 1:1:1 (90 mL) were slowly added a solution of LiOH.H2O solution (574 mg, 13.6 m mol) in water. After 4 h the mixture was concentrated, the residue was diluted with water and acidified to pH˜3 with 1 N HCl. The mixture was extracted with ethyl acetate, the extracts were dried over sodium sulfate and evaporated. The residue was triturated with hexane to give the title compound (3.6 g, 91.58%) as an off white solid. LC-MS: 759 (M+H).

Workup

  1. concentrationAfter 4 h the mixture was concentrated
  2. additionthe residue was diluted with water
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialthe extracts were dried over sodium sulfate
  5. customevaporated
  6. customThe residue was triturated with hexane

Sources & evidence

ORD record
ord-5501cc82b23e4b0db6bbdfa3b7077300
Source dataset
uspto-grants-2016_08
Patent number
US09409888B2

Reaction notes

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