Dichloromethane → (R)-Methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)propanoate

HRID 270741Notes

Reaction equation

HRID 270741 reaction equation
[NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5](/[CH:9]=[C:10](\[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])/[C:11]([O:13][CH3:14])=[O:12])=[CH:4][C:3]=1[CH3:25].ClCCl.[H][H]>CO>[NH2:1][C:2]1[C:3]([CH3:25])=[CH:4][C:5]([CH2:9][C@@H:10]([C:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[C:11]([O:13][CH3:14])=[O:12])=[CH:6][C:7]=1[CH3:8]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 66605272(Z)-Methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)acrylateHCID 178418361HCID 178418361, compound

Product 1

HCID 86605338(R)-Methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)propanoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A flame-dried 2 L Parr hydrogenation bottle was charged with (Z)-methyl 3-(4-amino-3,5-dimethylphenyl)-2-(benzyloxycarbonyl)acrylate (84.5 g, 239 mmol), dichloromethane (300 mL), and methanol (300 mL). The bottle was swirled so that a light brown suspension was formed. This was degassed by a flow of nitrogen for 30 min. To this was quickly added (−)-1,2-bis((2R,5R)-2,5-diethylphospholano)bezene(cyclooctadiene) rhodium (I) tetrafluoroborate ([(2R,5R)-Et-DuPhosRh]BF4) (2.11 g, 3.20 mmol). The bottle was immediately attached to a Parr Hydrogenator. After 5 cycles of hydrogen (60 psi) and vacuum, the bottle was pressurized to 65 psi and the suspension was agitated at room temperature for 16 h. The reaction had become homogeneous. The reaction mixture was concentrated, and the resulting residue purified by flash chromatography (silica gel, 1:9 ethyl acetate/dichloromethane) to give 82.9 g (98%). 1H-NMR (DMSO-d6) δ 2.04 (s, 6H), 2.65 (dd, J=13.4, 9.8 Hz, 1H), 2.82 (dd, J=13.7, 5.2 Hz, 1H), 3.62 (s, 3H), 4.15-4.10 (m, 1H), 4.41 (s, 2H), 5.00 (s, 2H), 6.68 (s, 2H), 7.37-7.28 (m, 5H), 7.70 (d, J=7.9 Hz, 1H); 13C-NMR (DMSO-d6) δ 17.7, 35.9, 51.7, 56.1, 65.3, 120.4, 124.0, 127.5, 127.7, 128.2, 128.3, 136.9, 142.6, 155.9, 172.5.

Workup

  1. customwas formed
  2. customThis was degassed by a flow of nitrogen for 30 min
  3. concentrationThe reaction mixture was concentrated
  4. customthe resulting residue purified by flash chromatography (silica gel, 1:9 ethyl acetate/dichloromethane)
  5. customto give 82.9 g (98%)

Sources & evidence

ORD record
ord-3cbdfdc3a4e84ba89ab5eb4ad3e2209e
Source dataset
uspto-grants-2008_11
Patent number
US07449586B2

Reaction notes

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