Water → HCID 118574033, compound

HRID 1055456Notes

Reaction equation

HRID 1055456 reaction equation
O[Li].O.O.[C:5]([O:9][C:10]([N:12]([CH3:54])[C@@H:13]([CH3:53])[C:14]([NH:16][C@H:17]1[CH2:23][O:22][C:21]2[C:24]([C:28](=[O:34])[N:29]([CH2:31][CH2:32][OH:33])[CH3:30])=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]([CH2:35][C:36]2[C:45]([O:46][CH3:47])=[CH:44][CH:43]=[C:42]3[C:37]=2[CH:38]=[CH:39][C:40]([C:48]([O:50]C)=[O:49])=[CH:41]3)[C:18]1=[O:52])=[O:15])=[O:11])([CH3:8])([CH3:7])[CH3:6]>CO.C([O-])(O)=O.[Na+]>[C:5]([O:9][C:10]([N:12]([CH3:54])[C@@H:13]([CH3:53])[C:14]([NH:16][C@H:17]1[CH2:23][O:22][C:21]2[C:24]([C:28](=[O:34])[N:29]([CH2:31][CH2:32][OH:33])[CH3:30])=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]([CH2:35][C:36]2[C:45]([O:46][CH3:47])=[CH:44][CH:43]=[C:42]3[C:37]=2[CH:38]=[CH:39][C:40]([C:48]([OH:50])=[O:49])=[CH:41]3)[C:18]1=[O:52])=[O:15])=[O:11])([CH3:7])([CH3:8])[CH3:6]

Participants

6

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrate2×HCID 118574215HCID 118574215, compound

Product 1

HCID 118574033HCID 118574033, compoundYield 74.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
50 °C

Procedure

LiOH.H2O (7.15 mg, 170 μmol, Eq: 2.00) and H2O (200 μl) were added to a solution of methyl 5-(((S)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-9-((2-hydroxyethyl)(methyl)carbamoyl)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoate (59 mg, 85.2 μmol, Eq: 1.00) in MeOH (2 mL) and the mixture heated to 50° C. After 4 h an additional portion of LiOH.H2O (2 mg, 48 μmol, Eq. 0.65) was added. After 1 h the mixture was diluted with sat. NaHCO3 and extracted with Et2O. The aqueous mixture was acidified to pH 2.0 with 1 N HCl, extracted with EtOAc and the combined organic extracts were washed with brine, dried over Na2SO4 and concentrated to afford 5-(((S)-3-((S)-2-(tert-butoxycarbonyl(methyl)amino)propanamido)-9-((2-hydroxyethyl)(methyl)carbamoyl)-4-oxo-3,4-dihydrobenzo[b][1,4]oxazepin-5(2H)-yl)methyl)-6-methoxy-2-naphthoic acid (43 mg, 74%) which was used without purification.

Workup

  1. extractionextracted with Et2O
  2. extractionextracted with EtOAc
  3. washthe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-83105735af1148f9a1519f1a25808d47
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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