Ethyl chloroformate → HCID 67200254, compound

HRID 550594Notes

Reaction equation

HRID 550594 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[NH:14][N:15]=[C:16]([NH2:17])[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.Cl[C:28]([O:30][CH2:31][CH3:32])=[O:29]>C1COCC1>[CH3:32][CH2:31][O:30][C:28]([N:15]1[C:16]([NH2:17])=[C:10]2[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12][C:11]2=[N:14]1)=[O:29]

Participants

5

Reactant 3

HCID 10928Ethyl chloroformateHCID 81531DiisopropylethylamineHCID 67201367tert-Butyl 3-amino-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate

Product 1

HCID 67200254HCID 67200254, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 94.1 g of 3-amino-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester in 1.7 L of THF were added 135 mL of N,N-diisopropylethylamine. A solution of 37.6 mL of ethyl chloroformate in 300 mL of THF was added dropwise at 0° C. during 75 min. The mixture was stirred at 0° C. for 30 min. then evaporated under vacuum. The residue was taken-up with 1 L of water and extracted with ethyl acetate. The combined organic extracts were washed with 500 mL brine, dried over sodium sulfate, and evaporated to dryness. The crude mixture of isomers was purified by silica gel flash-chromatography, using a starting 87:13 mixture of dichloromethane-ethyl acetate as eluant, and increasing gradually the percentage of ethyl acetate up to 50%. The fractions containing the same isomer were evaporated to give 61.6 g of 3-amino-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine-2,5-dicarboxylic acid 5-tert-butyl ester 2-ethyl ester.

Workup

  1. customthen evaporated under vacuum
  2. extractionextracted with ethyl acetate
  3. washThe combined organic extracts were washed with 500 mL brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness
  6. additionThe crude mixture of isomers
  7. customwas purified by silica gel flash-chromatography
  8. additiona starting 87:13 mixture of dichloromethane-ethyl acetate as eluant
  9. temperatureincreasing gradually the percentage of ethyl acetate up to 50%
  10. additionThe fractions containing the same isomer
  11. customwere evaporated

Sources & evidence

ORD record
ord-273a15ccb4364afc8e63ad78bdc1fe78
Source dataset
uspto-grants-2011_05
Patent number
US07947686B2

Reaction notes

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