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

HRID 447237Notes

Reaction equation

HRID 447237 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 mmoles), dichloromethane (300 mL), and methanol (300 mL). The bottle was swirled so that a light brown suspension was formed. The mixture was degassed using a flow of nitrogen for 30 min. To this was quickly added (−)-1,2-bis((2R,5R)-2,5-diethylphospholano)-benzene(cyclooctadiene) rhodium (I) tetrafluoroborate ([(2R,5R)-Et-DuPhosRh]BF4) (2.11 g, 3.20 mmoles). 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, 5.2Hz, 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. customThe mixture was degassed
  3. customfor 30 min
  4. concentrationThe reaction mixture was concentrated
  5. customthe resulting residue purified by flash chromatography (silica gel, 1:9 ethyl acetate/dichloromethane)
  6. customto give 82.9 g (98%)

Sources & evidence

ORD record
ord-a4fc48a1bda84bb7b99a4df6caaf3503
Source dataset
uspto-grants-2013_07
Patent number
US08481546B2

Reaction notes

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