Water → HCID 118574204, compound

HRID 1055454Notes

Reaction equation

HRID 1055454 reaction equation
O[Li].O.O.[C:5]([O:9][C:10]([N:12]([CH3:51])[C@@H:13]([CH3:50])[C:14]([NH:16][C@H:17]1[CH2:23][O:22][C:21]2[C:24]([C:28]([O:30]C)=[O:29])=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]([CH2:32][C:33]2[C:42]3[C:37](=[CH:38][C:39]([C:43]([O:45]C)=[O:44])=[CH:40][CH:41]=3)[CH:36]=[CH:35][C:34]=2[O:47][CH3:48])[C:18]1=[O:49])=[O:15])=[O:11])([CH3:8])([CH3:7])[CH3:6]>CO>[C:5]([O:9][C:10]([N:12]([CH3:51])[C@@H:13]([CH3:50])[C:14]([NH:16][C@H:17]1[CH2:23][O:22][C:21]2[C:24]([C:28]([OH:30])=[O:29])=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]([CH2:32][C:33]2[C:42]3[C:37](=[CH:38][C:39]([C:43]([OH:45])=[O:44])=[CH:40][CH:41]=3)[CH:36]=[CH:35][C:34]=2[O:47][CH3:48])[C:18]1=[O:49])=[O:15])=[O:11])([CH3:8])([CH3:7])[CH3:6]

Participants

5

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrate2×HCID 118574391HCID 118574391, compound

Product 1

HCID 118574204HCID 118574204, compoundYield 28.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

LiOH.H2O (22.0 mg, 523 μmol, Eq: 2.00) and H2O (0.5 mL) was added to a solution of (S)-methyl 3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-5-((2-methoxy-6-(methoxycarbonyl)naphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepine-9-carboxylate (170 mg, 262 μmol, Eq: 1.00) in MeOH (5 mL). The mixture was heated to 50° C. After 3.5 h, LiOH.H2O (44 mg, 1.04 mmol) was added and temperature increased to 60° C. After 1.5 h, the MeOH was removed under vacuum, the aqueous mixture diluted with water and extracted with Et2O. The aqueous mixture was acidified to pH 2.0 with 1 N HCl and extracted with EtOAc. The combined organic extracts were washed brine and concentrated to give a residue that was triturated with Et2O to afford (S)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-5-((6-carboxy-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepine-9-carboxylic acid (47 mg) as a white solid.

Workup

  1. temperaturetemperature increased to 60° C
  2. waitAfter 1.5 h
  3. customthe MeOH was removed under vacuum
  4. additionthe aqueous mixture diluted with water
  5. extractionextracted with Et2O
  6. extractionextracted with EtOAc
  7. washThe combined organic extracts were washed brine
  8. concentrationconcentrated
  9. customto give a residue that
  10. customwas triturated with Et2O

Sources & evidence

ORD record
ord-38dd5ebe9f3341d6b60226233283b54e
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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