1,2-Dichloroethane → HCID 71699197, compound

HRID 518231Notes

Reaction equation

HRID 518231 reaction equation
CO[C:3](=[O:31])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[CH:8][C:9]2[O:27][C:13]3([CH2:18][CH2:17][N:16]([CH2:19][C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[CH2:15][CH2:14]3)[N:12]([CH3:28])[C:11](=[O:29])[C:10]=2[CH:30]=1.[OH-].[Na+].Cl.C(Cl)C[Cl:37].C1C=CC2[N:47]([OH:48])N=NC=2C=1.NOC1CCCCO1>O1CCOCC1.O>[ClH:37].[F:26][C:23]1[CH:22]=[CH:21][C:20]([CH2:19][N:16]2[CH2:17][CH2:18][C:13]3([N:12]([CH3:28])[C:11](=[O:29])[C:10]4[CH:30]=[C:6](/[CH:5]=[CH:4]/[C:3]([NH:47][OH:48])=[O:31])[CH:7]=[CH:8][C:9]=4[O:27]3)[CH2:14][CH2:15]2)=[CH:25][CH:24]=1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 66932392HCID 66932392, compound

Product 1

HCID 71699197HCID 71699197, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

(E)-3-{1′-(4-Fluoro-benzyl)-3,4-dihydro-3-methyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-acrylic acid methyl ester (520 mg, 1.22 mmol) was suspended in dioxane (20 ml) and water (10 ml). 1 M NaOH (1.59 ml) was added and the resulting mixture was stirred at RT for 5 h. The mixture was neutralized with 1 M HCl and the solvent was removed. The resulting acid was dissolved in DCM (10 ml) and TEA (0.338 ml, 2.44 mmol). EDC (350 mg, 1.83 mmol), HOBT (247 mg, 1.83 mmol) and NH2OTHP (172 mg, 1.46 mmol) were added to the resulting solution. The mixture was stirred for 6 h at RT and then partitioned between 5% aqueous NaHCO3 and DCM. The organic layer was dried over Na2SO4 and evaporated. The crude product was purified by column chromatography (eluent: DCM/MeOH 97:3) and the resulting compound was dissolved in DCM and treated with 4 M HCl in dioxane for 4 h. The precipitate was filtered to give (E)-3-{1′-(4-fluoro-benzyl)-3,4-dihydro-3-methyl-4-oxo-spiro[2H-(1,3)-benzoxazine-2,4′-piperidin]-6-yl}-N-hydroxy-acrylamide hydrochloride (451 mg) as a white solid.

Workup

  1. customthe solvent was removed
  2. dissolutionThe resulting acid was dissolved in DCM (10 ml)
  3. stirringThe mixture was stirred for 6 h at RT
  4. custompartitioned between 5% aqueous NaHCO3 and DCM
  5. dry with materialThe organic layer was dried over Na2SO4
  6. customevaporated
  7. customThe crude product was purified by column chromatography (eluent: DCM/MeOH 97:3)
  8. dissolutionthe resulting compound was dissolved in DCM
  9. additiontreated with 4 M HCl in dioxane for 4 h
  10. filtrationThe precipitate was filtered

Sources & evidence

ORD record
ord-72b6f14ee3004d2e8b30a2ce044e3db5
Source dataset
uspto-grants-2015_08
Patent number
US09115148B2

Reaction notes

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