Lithium Hydroxide → 2-[(3S)-7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetic acid

HRID 1054173Notes

Reaction equation

HRID 1054173 reaction equation
[Li+].[OH-].[Cl:3][C:4]1[CH:32]=[CH:31][C:7]2[N:8]([C:18]([C:20]3[CH:21]=[CH:22][C:23]4[O:28][CH2:27][C:26](=[O:29])[NH:25][C:24]=4[CH:30]=3)=[O:19])[C@@H:9]([CH2:12][C:13]([O:15]CC)=[O:14])[CH2:10][O:11][C:6]=2[CH:5]=1.CCOC(C)=O>O.C1COCC1>[Cl:3][C:4]1[CH:32]=[CH:31][C:7]2[N:8]([C:18]([C:20]3[CH:21]=[CH:22][C:23]4[O:28][CH2:27][C:26](=[O:29])[NH:25][C:24]=4[CH:30]=3)=[O:19])[C@@H:9]([CH2:12][C:13]([OH:15])=[O:14])[CH2:10][O:11][C:6]=2[CH:5]=1

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 8857Ethyl AcetateHCID 131736330(S)-ethyl {7-chloro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetate2×

Product 1

HCID 1185997562-[(3S)-7-chloro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetic acidYield 107%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

LiOH (1.40 g, 58.3 mmol) was dissolved in water (50 mL) and added to (S)-ethyl {7-chloro-4-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-3,4-dihydro-2H-1,4-benzoxazin-3-yl}acetate (Intermediate 21a, 5.71 g, 11.7 mmol) in THF (50 mL). The reaction mixture was stirred at rt for 75 min EtOAc (150 mL) was added. Washed with HCl (1 M, 100+50 mL) and brine (50 mL). The organic phase was dried over Na2SO4 and after filtration the solvents were evaporated in vacuo to yield the crude the title compound (82 mg, 107%) which was used further in the synthesis of Example 5a.

Workup

  1. additionwas added
  2. washWashed with HCl (1 M, 100+50 mL) and brine (50 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationafter filtration the solvents
  5. customwere evaporated in vacuo

Sources & evidence

ORD record
ord-dc3dd8d35e0e4d23ba92c2b734f3c18d
Source dataset
uspto-grants-2016_07
Patent number
US09394291B2

Reaction notes

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