Benzyl chloroformate → HCID 86590129, compound

HRID 1840516Notes

Reaction equation

HRID 1840516 reaction equation
[CH3:1][C:2]([CH3:22])([O:4][C:5]([NH:7][C@@H:8]([CH2:13][C:14]#[C:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)[C:9]([O:11][CH3:12])=[O:10])=[O:6])[CH3:3].[H][H].C(=O)([O-])O.[Na+].Cl[C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32]>C(O)C.C(O)(=O)C.O1CCCC1.O.C(OCC)(=O)C.[Pd].[Pt]=O>[CH3:3][C:2]([CH3:22])([O:4][C:5]([NH:7][C@@H:8]([CH2:13][CH2:14][CH2:15][CH:16]1[CH2:21][CH2:20][N:19]([C:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:32])[CH2:18][CH2:17]1)[C:9]([O:11][CH3:12])=[O:10])=[O:6])[CH3:1]

Participants

12

Reactant 4

HCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 86590130HCID 86590130, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 86590129HCID 86590129, compoundYield 79.1%

Reagents, catalysts & solvents 7

HCID 23938PalladiumCatalystHCID 82844Platinum oxide (PtO)CatalystHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2.8 g (10.0 mmol) of methyl (S)-2-[[(1,1-dimethylethoxy)carbonyl]amino]-5-pyrid-4-ylpent-4-ynoate and 0.28 g of active 10% palladium-on-charcoal in 20 ml of ethanol is stirred for 3 hours at room temperature under 60 psi of hydrogen. The reaction mixture is filtered and concentrated under reduced pressure. The residue obtained is taken up in 20 ml of acetic acid and stirred for 14 hours in the presence of 0.05 g of platinum oxide, under 60 psi of hydrogen. The reaction mixture is filtered and then concentrated under reduced pressure. The residue obtained is taken up in 10 ml of tetrahydrofuran (THF) and 5 ml of water. This solution is cooled to 0° C., followed by addition of a solution of 3.4 g (40.0 mmol) of sodium hydrogen carbonate in 40 ml of water, and 1.63 ml (12.0 mmol) of benzyl chloroformate are added dropwise. The mixture is allowed to warm to room temperature and the reaction is continued for 4 hours. The reaction mixture is taken up in 200 ml of ethyl acetate and is washed twice with 100 ml of 1N hydrochloric acid solution and then with 100 ml of saturated sodium hydrogen carbonate solution and with 100 ml of saturated sodium chloride solution. The resulting solution is dried over sodium sulphate. The resulting product is filtered and concentrated. The residue obtained is purified by chromatography on a column of silica gel, eluting under pressure with a cyclohexane/ethyl acetate gradient of from 95/5 to 80/20. 3.55 g of methyl (S)-α-[[(1,1-dimethylethoxy)carbonyl]amino]-1-[(phenylmethoxy)carbonyl]piperidine-4-pentanoate are obtained in the form of a viscous oil.

Workup

  1. filtrationThe reaction mixture is filtered
  2. concentrationconcentrated under reduced pressure
  3. customThe residue obtained
  4. filtrationThe reaction mixture is filtered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue obtained
  7. additionare added dropwise
  8. temperatureto warm to room temperature
  9. washis washed twice with 100 ml of 1N hydrochloric acid solution
  10. dry with materialThe resulting solution is dried over sodium sulphate
  11. filtrationThe resulting product is filtered
  12. concentrationconcentrated
  13. customThe residue obtained
  14. customis purified by chromatography on a column of silica gel
  15. washeluting under pressure with a cyclohexane/ethyl acetate gradient of from 95/5 to 80/20

Sources & evidence

ORD record
ord-b3f8187a308d4346b93100bed5c9e9c9
Source dataset
uspto-grants-2004_01
Patent number
US06680329B2

Reaction notes

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