Methanol → 1-benzyl 4-methyl (2S)-2-aminobutanedioate

HRID 18368Notes

Reaction equation

HRID 18368 reaction equation
O=S(Cl)Cl.[NH2:5][C@H:6]([C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[CH2:7][C:8]([OH:10])=[O:9].[CH3:21]O>>[NH2:5][C@@H:6]([CH2:7][C:8]([O:10][CH3:21])=[O:9])[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12]

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 6994684H-Asp-OBzl

Product 1

HCID 129676051-benzyl 4-methyl (2S)-2-aminobutanedioate

Procedure

SOCl2 (6.60 mL, 90.5 mmol) was added drop-wise over 15 min to a cooled (ice-water) mixture of (S)-3-amino-4-(benzyloxy)-4-oxobutanoic acid (10.04 g, 44.98 mmol) and MeOH (300 mL), the cooling bath was removed and the reaction mixture was stirred at ambient condition for 29 hr. Most of the volatile component was removed in vacuo and the residue was carefully partitioned between EtOAc (150 mL) and saturated NaHCO3 solution. The aqueous phase was extracted with EtOAc (150 mL, 2×), and the combined organic phase was dried (MgSO4), filtered, and concentrated in vacuo to afford (S)-1-benzyl 4-methyl 2-aminosuccinate as a colorless oil (9.706 g). 1H NMR (DMSO-d6, δ=2.5 ppm, 400 MHz): δ 7.40-7.32 (m, 5H), 5.11 (s, 2H), 3.72 (app t, J=6.6, 1H), 3.55 (s, 3H), 2.68 (dd, J=15.9, 6.3, 1H), 2.58 (dd, J=15.9, 6.8, 1H), 1.96 (s, 2H). LC (Cond. 1): RT=0.90 min; LC/MS: Anal. Calcd. for [M+H]+ C12H16NO4: 238.11. found 238.22.

Workup

  1. temperaturea cooled
  2. customthe cooling bath was removed
  3. customMost of the volatile component was removed in vacuo
  4. customthe residue was carefully partitioned between EtOAc (150 mL) and saturated NaHCO3 solution
  5. extractionThe aqueous phase was extracted with EtOAc (150 mL, 2×)
  6. dry with materialthe combined organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d739edadda524ba5a4396965c0724bec
Source dataset
uspto-grants-2010_06
Patent number
US07741347B2

Reaction notes

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