Lithium hydroxide, monohydrate → 5-(((S)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoic acid

HRID 1055441Notes

Reaction equation

HRID 1055441 reaction equation
O[Li].O.[C:4]([O:8][C:9]([N:11]([CH3:46])[C@@H:12]([CH3:45])[C:13]([NH:15][C@H:16]1[CH2:22][O:21][C:20]2[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=2[N:18]([CH2:27][C:28]2[C:37]([O:38][CH3:39])=[CH:36][CH:35]=[C:34]3[C:29]=2[CH:30]=[CH:31][C:32]([C:40]([O:42]C)=[O:41])=[CH:33]3)[C:17]1=[O:44])=[O:14])=[O:10])([CH3:7])([CH3:6])[CH3:5].OS([O-])(=O)=O.[K+]>O.CO>[C:4]([O:8][C:9]([N:11]([CH3:46])[C@@H:12]([CH3:45])[C:13]([NH:15][C@H:16]1[CH2:22][O:21][C:20]2[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=2[N:18]([CH2:27][C:28]2[C:37]([O:38][CH3:39])=[CH:36][CH:35]=[C:34]3[C:29]=2[CH:30]=[CH:31][C:32]([C:40]([OH:42])=[O:41])=[CH:33]3)[C:17]1=[O:44])=[O:14])=[O:10])([CH3:6])([CH3:7])[CH3:5]

Participants

6

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 516920Potassium bisulfateHCID 118574109methyl 5-(((S)-3-((S)-2-(tert-butoxycarbonyl (methyl)amino)propanamido)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoate

Product 1

HCID 1185741935-(((S)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoic acidYield 93.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

LiOH.H2O (24.0 mg, 573 μmol, Eq: 3) was dissolved in water and the solution was added to a solution of methyl 5-(((S)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoate (113 mg, 191 μmol, Eq: 1.00) in MeOH (3 mL) and the mixture was heated to 50° C. for 1 h and then to 60° C. for 1 h. The mixture was cooled, KHSO4 solution was added and the mixture extracted with EtOAc. The combined extracts were concentrated and the residue purified by silica gel chromatography to afford 5-(((S)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoic acid (103 mg, 93%) as a white powder.

Workup

  1. temperatureThe mixture was cooled
  2. extractionthe mixture extracted with EtOAc
  3. concentrationThe combined extracts were concentrated
  4. customthe residue purified by silica gel chromatography

Sources & evidence

ORD record
ord-019a6b1f7b8840ffb9002e6624ba5615
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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