Potassium Carbonate → (S)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one

HRID 2046189Notes

Reaction equation

HRID 2046189 reaction equation
C(OC([N:8]1[C@@H:12]([CH2:13][N:14]2[C:18]([C:19](OCC)=[O:20])=[CH:17][C:16]([CH2:24][O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:15]2)[CH2:11][O:10]C1(C)C)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>Cl.O1CCOCC1.C(Cl)Cl>[OH:10][CH2:11][C@@H:12]1[CH2:13][N:14]2[N:15]=[C:16]([CH2:24][O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:17]=[C:18]2[C:19](=[O:20])[NH:8]1

Participants

6

Reactant 2

HCID 11430Potassium CarbonateHCID 70654325(S)-4-(5-Ethoxycarbonyl-3-phenoxymethyl-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 67974237(S)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-oneYield 63.6%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

(S)-4-(5-Ethoxycarbonyl-3-phenoxymethyl-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (0.91 g, 1.9 mmol) was dissolved in a 4M solution of HCl in dioxane (9.8 mL) and the solution was stirred at room temperature for 1 hour. The solvent was evaporated in vacuo and the residue was taken up in MeOH (10 mL) and K2CO3 (0.82 g, 5.96 mmol) was added. The mixture was stirred at 100° C. for 5 minutes under microwave irradiation. Then mixture was diluted with DCM. The solid was filtered off and the filtrate solvent was evaporated in vacuo. The residue was purified by flash column chromatography (silica, MeOH in AcOEt 0/100 to 10/90). Desired fractions were collected and the solvents evaporated in vacuo to yield (S)-6-hydroxymethyl-2-phenoxymethyl-6,7-dihydro-5H-pyrazolo[1,5-a]pyrazin-4-one (0.33 g, 61% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.27-3.33 (m, 1H), 3.46-3.54 (m, 1H), 3.73-3.84 (m, 1H), 4.30 (dd, J=13.4, 5.8 Hz, 1H), 4.38 (dd, J=12.9, 5.3 Hz, 1H), 5.05 (s, 2H), 5.18 (br. s., 1H), 6.77 (s, 1H), 6.91-6.98 (m, 1H), 6.99-7.07 (m, 2H), 7.25-7.35 (m, 2H), 8.26 (d, J=2.5 Hz, 1H).

Workup

  1. customThe solvent was evaporated in vacuo
  2. stirringThe mixture was stirred at 100° C. for 5 minutes under microwave irradiation
  3. filtrationThe solid was filtered off
  4. customthe filtrate solvent was evaporated in vacuo
  5. customThe residue was purified by flash column chromatography (silica, MeOH in AcOEt 0/100 to 10/90)
  6. customDesired fractions were collected
  7. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-e9c1045feefe467ebd6d93ca000389e2
Source dataset
uspto-grants-2013_11
Patent number
US08592422B2

Reaction notes

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