Sodium Hydroxide → 5-(tert-Butoxycarbonyl)-6-cyclopropyl-2-iodo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxylic acid

HRID 920829Notes

Reaction equation

HRID 920829 reaction equation
[CH:1]1([CH:4]2[CH2:9][N:8]3[N:10]=[C:11]([I:18])[C:12]([C:13]([O:15]CC)=[O:14])=[C:7]3[CH2:6][N:5]2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:3][CH2:2]1.[OH-].[Na+]>C(O)C.O.C(Cl)Cl>[C:22]([O:21][C:19]([N:5]1[CH:4]([CH:1]2[CH2:2][CH2:3]2)[CH2:9][N:8]2[N:10]=[C:11]([I:18])[C:12]([C:13]([OH:15])=[O:14])=[C:7]2[CH2:6]1)=[O:20])([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 1180620475-tert-Butyl 3-ethyl 6-cyclopropyl-2-iodo-6,7-dihydropyrazolo[1,5-a]pyrazine-3,5(4H)-dicarboxylate

Product 1

HCID 1180623275-(tert-Butoxycarbonyl)-6-cyclopropyl-2-iodo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxylic acidYield 94%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of Intermediate 348E (0.85 g, 1.843 mmol) in ethanol (2 mL) and water (1 mL) was added NaOH (0.369 g, 9.21 mmol) and the resulting solution was stirred at RT for 10 h. The reaction mixture was diluted with DCM (10 mL) and washed successively with an aqueous solution of 1N HCl, water and brine. The organic layer was then dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure to afford the Intermediate 348F as an off-white solid (0.75 g, 94%). MS(ES): m/z=434 [M+H]+; 1H NMR (300 MHz, DMSO-d6) δ ppm 12.6 (br. s., 1H), 5.11 (d, J=18.89 Hz, 1H), 4.45 (d, J=18.51 Hz, 1H), 4.16-4.25 (m, 2H), 3.82 (br. s., 1H), 1.43 (s, 9H), 0.82-0.96 (m, 1H), 0.47 (d, J=7.93 Hz, 2H), 0.35 (dd, J=6.80, 4.91 Hz, 2H).

Workup

  1. washwashed successively with an aqueous solution of 1N HCl, water and brine
  2. dry with materialThe organic layer was then dried over Na2SO4
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under reduced pressure

Sources & evidence

ORD record
ord-8bc8b62bc52f4c7f98d4a066f0b757e7
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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