Water → HCID 118574245, compound

HRID 1055451Notes

Reaction equation

HRID 1055451 reaction equation
O[Li].O.O.[C:5]([O:9][C:10]([N:12]([CH3:47])[C@@H:13]([CH3:46])[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][CH:39]=[CH:40][CH:41]=3)[CH:36]=[CH:35][C:34]=2[O:43][CH3:44])[C:18]1=[O:45])=[O:15])=[O:11])([CH3:8])([CH3:7])[CH3:6]>CO>[C:5]([O:9][C:10]([N:12]([CH3:47])[C@@H:13]([CH3:46])[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][CH:39]=[CH:40][CH:41]=3)[CH:36]=[CH:35][C:34]=2[O:43][CH3:44])[C:18]1=[O:45])=[O:15])=[O:11])([CH3:8])([CH3:7])[CH3:6]

Participants

5

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrate2×HCID 118574255HCID 118574255, compound

Product 1

HCID 118574245HCID 118574245, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

LiOH.H2O (9.1 mg, 217 μmol, Eq: 1.5) and H2O (1 mL) were added to a solution of (S)-methyl 3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-5-((2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepine-9-carboxylate (95 mg, 145 μmol, Eq: 1.00) in MeOH (4 mL). The mixture was heated to 50° C. After 2 h, LiOH.H2O (18 mg, 429 μmol, Eq: 2.95) was added and the temperature was increased to 60° C. After 4 h, the mixture was concentrated to a volume of approximately 1.5 mL. This mixture was acidified to pH 2 with 1 N HCl and extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 filtered and concentrated to give a material that was purified by silica gel chromatography to afford (S)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-5-((2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepine-9-carboxylic acid (31 mg, 37%) as an off-white foam.

Workup

  1. temperaturethe temperature was increased to 60° C
  2. waitAfter 4 h
  3. concentrationthe mixture was concentrated to a volume of approximately 1.5 mL
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a material that
  10. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-0f6b5369e22f4a4abe12257fa712e605
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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