Benzyl chloroformate → HCID 57828239, compound

HRID 1644216Notes

Reaction equation

HRID 1644216 reaction equation
[Si:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([C:19]#[C:20][CH2:21][CH2:22][NH:23][C:24](=[O:33])[O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].ClC(OCC1C=CC=CC=1)=O>CO.C(Cl)Cl.C([O-])(O)=O.[Na+].[Pd]>[Si:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12]([CH2:19][CH2:20][CH2:21][CH2:22][NH:23][C:24](=[O:33])[O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 10387Benzyl chloroformateHCID 57828236HCID 57828236, compound

Product 1

HCID 57828239HCID 57828239, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 23716255Sodium bicarbonate methylene chlorideSolvent

Procedure

A solution of carbamate 18 (2.0 g, 4.3 mmole) and 10% Pd/C (300 mg) in MeOH (60 mL) was subjected to hydrogenation conditions (50 psi) for 8 h at room temperature. The reaction mixture was filtered through a plug of diatomaceous earth and the plug was washed with MeOH (2×20 mL). The filtrate was then concentrated in vacuo to afford crude amine (1.4 g) which was dissolved in 1:1 CH2Cl2/NaHCO3 (saturated solution) (30 mL). Benzyl chloroformate (0.62 mL) was added dropwise at room temperature and the reaction mixture was stirred for 1 h. The mixture was concentrated, the residue was dissolved in EtOAc (500 mL), and the solution was washed with water (300 mL) and brine (300 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (silica gel, 4:1 hexanes/EtOAc) to afford butylcarbamate 19 (1.5 g, 77%) as a light yellow oil: 1H NMR (300 MHz, DMSO-d6) δ 8.24 (m, 1H), 7.91 (d, J=7.4 Hz, 1H), 7.51-7.42 (m, 2H), 7.34-7.28 (m, 5H), 7.12 (d, J=7.6 Hz, 1H), 6.77 (d, J=7.6 Hz, 1H), 5.08 (br s, 2H), 4.75 (br s, 1H), 3.22 (q, J=6.4 Hz, 2H), 2.99 (q, J=7.4 Hz, 2H), 1.76-1.71 (m, 2H), 1.67-1.56 (m, 2H), 1.09 (s, 9H), 0.27 (s, 6H).

Workup

  1. filtrationThe reaction mixture was filtered through a plug of diatomaceous earth
  2. washthe plug was washed with MeOH (2×20 mL)
  3. concentrationThe filtrate was then concentrated in vacuo
  4. customto afford crude amine (1.4 g) which
  5. concentrationThe mixture was concentrated
  6. dissolutionthe residue was dissolved in EtOAc (500 mL)
  7. washthe solution was washed with water (300 mL) and brine (300 mL)
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by column chromatography (silica gel, 4:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-38d80b662cc24fdebec79503e3c10f72
Source dataset
uspto-grants-2012_02
Patent number
US08124607B2

Reaction notes

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