Formic Acid → (R)-7-[2-((Z)-3-diethylaminoprop-1-en-1-yl)-4-fluorobenzenesulfonyl-amino]-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylic acid

HRID 715934Notes

Reaction equation

HRID 715934 reaction equation
[CH2:1]([N:3]([CH2:35][CH3:36])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[C:30]([C:31]([O:33]C)=[O:32])=[C:22]2[O:23][CH2:24][C@H:25]3[CH2:29][CH2:28][CH2:27][N:26]3[C:21]2=[CH:20][CH:19]=1)(=[O:16])=[O:15])[CH3:2].O.[OH-].[Li+].C(O)=O.C(OCC)(=O)C>O1CCOCC1.O.C(O)C.C1(C)C=CC=CC=1>[CH2:35]([N:3]([CH2:1][CH3:2])[CH2:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[S:14]([NH:17][C:18]1[C:30]([C:31]([OH:33])=[O:32])=[C:22]2[O:23][CH2:24][C@H:25]3[CH2:29][CH2:28][CH2:27][N:26]3[C:21]2=[CH:20][CH:19]=1)(=[O:15])=[O:16])[CH3:36]

Participants

9

Reactant 4

HCID 284Formic AcidHCID 8857Ethyl AcetateHCID 168937Lithium hydroxide, monohydrateHCID 86712100methyl (R)-7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzene-sulfonylamino]-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate2×

Product 1

HCID 71472376(R)-7-[2-((Z)-3-diethylaminoprop-1-en-1-yl)-4-fluorobenzenesulfonyl-amino]-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylic acidYield 48%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl (R)-7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzene-sulfonylamino]-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylate (Intermediate 1, 0.640 g) and lithium hydroxide monohydrate (0.505 g) in dioxane (9.6 mL) and water (2.4 mL) was irradiated in the microwave at 135° C. for 45 minutes. After cooling, the mixture was acidified with formic acid, diluted with ethanol and toluene and concentrated in vacuo. The residue was triturated with methanol in DCM (10% solution) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-10%. The resultant solid was triturated with ethyl acetate to give a pale yellow solid which was treated with hot ethyl acetate and filtered while still hot. The filtrate was concentrated in vacuo and the residue was triturated with ethyl acetate to give (R)-7-[2-((Z)-3-diethylaminoprop-1-en-1-yl)-4-fluorobenzenesulfonyl-amino]-2,3,3a,4-tetrahydro-1H-benzo[b]pyrrolo[1,2-d][1,4]oxazine-6-carboxylic acid (0.299 g) as a pale yellow solid.

Workup

  1. customwas irradiated in the microwave at 135° C. for 45 minutes
  2. temperatureAfter cooling
  3. concentrationconcentrated in vacuo
  4. customThe residue was triturated with methanol in DCM (10% solution)
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by chromatography on silica
  8. washeluting with a mixture of methanol and DCM with a gradient of 0-10%
  9. customThe resultant solid was triturated with ethyl acetate
  10. customto give a pale yellow solid which
  11. filtrationfiltered while still hot
  12. concentrationThe filtrate was concentrated in vacuo
  13. customthe residue was triturated with ethyl acetate

Sources & evidence

ORD record
ord-bcfdd936a82149469448c6d4ade9a6dd
Source dataset
uspto-grants-2015_11
Patent number
US09187494B2

Reaction notes

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