m-Chloroperbenzoic acid → Methyl 8-[bis-(tert-butoxycarbonyl)amino]-6-hydroxy-5,6-dihydro-pyrazolo[5,1-a]isoquinoline-7-carboxylate

HRID 595106Notes

Reaction equation

HRID 595106 reaction equation
[C:1]([O:5][C:6]([N:8]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[C:13]([CH:19]=[CH2:20])[C:12]([C:21]2[NH:22][N:23]=[CH:24][CH:25]=2)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N+]1([O-])CC[O:37]CC1.ClC1C=CC=C(C(OO)=O)C=1>C(Cl)Cl.CC(C1C=C(C=N[C@@H]2[C@@H](N=CC3C([O-])=C(C(C)(C)C)C=C(C(C)(C)C)C=3)CCCC2)C([O-])=C(C(C)(C)C)C=1)(C)C.[Cl-].[Mn+3]>[C:29]([O:28][C:26]([N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C:9]1[CH:10]=[CH:11][C:12]2[C:21]3=[CH:25][CH:24]=[N:23][N:22]3[CH2:20][CH:19]([OH:37])[C:13]=2[C:14]=1[C:15]([O:17][CH3:18])=[O:16])=[O:27])([CH3:32])([CH3:31])[CH3:30]

Participants

6

Reactant 3

HCID 70297m-Chloroperbenzoic acidHCID 82029Methyl morpholine oxideHCID 86712817methyl 6-[bis-(tert-butoxycarbonyl)amino]-3-(2H-pyrazol-3-yl)-2-vinylbenzoate2×

Product 1

HCID 71005652Methyl 8-[bis-(tert-butoxycarbonyl)amino]-6-hydroxy-5,6-dihydro-pyrazolo[5,1-a]isoquinoline-7-carboxylateYield 11.7%

Reagents, catalysts & solvents 2

HCID 10211480(S,S)-[N,N'-Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine]manganese(III) chlorideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled solution of methyl 6-[bis-(tert-butoxycarbonyl)amino]-3-(2H-pyrazol-3-yl)-2-vinylbenzoate (Intermediate 9, 2.4 g) in anhydrous DCM (100 mL) at 0° C. was added (S,S)-(+)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamino manganese (III) chloride (0.280 g) and N-methylmorpholine N-oxide (3.2 g). m-Chloroperbenzoic acid (3.8 g) was then added portionwise and the reaction mixture was stirred at 0° C. for 20 minutes. The resultant mixture was quenched by the addition of 2M aqueous sodium carbonate solution and the organic layer was separated, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and DCM with a gradient of 0-100%. The resultant material was repurified by chromatography on silica, eluting with a mixture of ethyl acetate and DCM with a gradient of 0-100% to give methyl 8-[bis-(tert-butoxycarbonyl)amino]-6-hydroxy-5,6-dihydro-pyrazolo[5,1-a]isoquinoline-7-carboxylate (0.290 g).

Workup

  1. customThe resultant mixture was quenched by the addition of 2M aqueous sodium carbonate solution
  2. customthe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by chromatography on silica
  7. washeluting with a mixture of ethyl acetate and DCM with a gradient of 0-100%
  8. customThe resultant material was repurified by chromatography on silica
  9. washeluting with a mixture of ethyl acetate and DCM with a gradient of 0-100%

Sources & evidence

ORD record
ord-5426ed3f692e412ea4aa6a3a59f5736a
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

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