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

HRID 1476025Notes

Reaction equation

HRID 1476025 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-bed8058a2a4e407f8c81cc5dd0b70572
Source dataset
uspto-grants-2015_04
Patent number
US09018390B2

Reaction notes

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