(Z)-2-[[(phenylmethoxy)amino]methyl]-2-hexenoic acid methyl ester → 2-[[(Phenylmethoxy)amino]methyl]-(2S)-hexanoic acid methyl ester

HRID 271972Notes

Reaction equation

HRID 271972 reaction equation
[CH3:1][O:2][C:3](=[O:19])/[C:4](/[CH2:9][NH:10][O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[CH:5]\[CH2:6][CH2:7][CH3:8]>[B-](F)(F)(F)F.C1C2C=CC1C=C2.C1C2C=CC1C=C2.[Rh]>[CH3:1][O:2][C:3](=[O:19])[C@H:4]([CH2:9][NH:10][O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[CH2:5][CH2:6][CH2:7][CH3:8]

Participants

3

Reactant 1

HCID 101440200(Z)-2-[[(phenylmethoxy)amino]methyl]-2-hexenoic acid methyl ester

Product 1

HCID 876299142-[[(Phenylmethoxy)amino]methyl]-(2S)-hexanoic acid methyl esterYield 94.5%

Reagents, catalysts & solvents 1

HCID 10915722Bis(norbornadiene)rhodium(I) tetrafluoroborateCatalyst

Procedure

A ˜1:1 mixture of (E) and (Z)-2-[[(phenylmethoxy)amino]methyl]-2-hexenoic acid methyl ester (3.95 g, 15 mmol), bis(norbornadiene)rhodium(I)tetrafluoroborate (56.1 mg, 0.15 mmol) and (1S,1′S,2R,2′R)-TangPhos (47.3 mg, 0.165 mmol) in de-oxygenated methanol (90 mL) in a Parr bottle is hydrogenated under H2 (45-55 psi) at RT for 24 hours. The reaction mixture is concentrated on Rotavap under reduced pressure (20 mbar) until no further solvent distills. The residue liquid is dissolved in a mixture of ethyl acetate/heptane (50/50, 10 mL) and filtered through a silica gel pad (˜12 g). The silica gel pad is rinsed with a mixture of ethyl acetate/heptane (50/50, 200 mL). The filtrates are combined and concentrated on Rotavap under reduced pressure (20 mbar) until no further solvent distills to afford 2-[[(phenylmethoxy)amino]methyl]-(2S)-hexanoic acid methyl ester (3.76 g, yield: 94%, S:R=98.0:2.0) as a liquid.

Workup

  1. concentrationThe reaction mixture is concentrated on Rotavap under reduced pressure (20 mbar) until no further solvent
  2. distillationdistills
  3. dissolutionThe residue liquid is dissolved in a mixture of ethyl acetate/heptane (50/50, 10 mL)
  4. filtrationfiltered through a silica gel pad (˜12 g)
  5. washThe silica gel pad is rinsed with a mixture of ethyl acetate/heptane (50/50, 200 mL)
  6. concentrationconcentrated on Rotavap under reduced pressure (20 mbar) until no further solvent
  7. distillationdistills

Sources & evidence

ORD record
ord-cde579d827434955bb8eb11393a12118
Source dataset
uspto-grants-2008_11
Patent number
US07452999B2

Reaction notes

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