Methyl iodide → HCID 67398506, compound

HRID 1526410Notes

Reaction equation

HRID 1526410 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][C@H:11]([CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:12]([OH:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23]([O-])(O)=O.[Na+].CI>CC(N(C)C)=O>[CH2:1]([O:8][CH2:9][CH2:10][C@H:11]([CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:12]([O:14][CH3:23])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 516892Sodium Bicarbonate2×HCID 67396939HCID 67396939, compound

Product 1

HCID 67398506HCID 67398506, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of (R)-2-(2-(benzyloxy)ethyl)-4-tert-butoxy-4-oxobutanoic acid (120 g, 388 mmol) in DMA (750 mL) was added NaHCO3 (65.2 g, 776 mmol) followed by MeI (36.4 mL, 582 mmol) and stirred overnight at room temperature. Additional NaHCO3 (130 g, 1.55 mol), and MeI (72.8 mL, 1.16 mol) were added and stirring was continuted for an additional 20 h. The mixture was filtered and the filtrate partitioned between MTBE (1.5 L) and H2O (1.5 L). The aqueous phase was separated and back-extracted with MTBE (1.0 L). The combined organics were washed with H2O (2×1.5 L), brine (1 L), dried over MgSO4, and filtered. The filtrate was concentrated to give a pale yellow oil containing (R)-4-tert-butyl 1-methyl 2-(2-(benzyloxy)ethyl)succinate (140 g, 379 mmol, 98% yield). Exact mass calculated for C18H26O5: 322.2, found: LCMS m/z=323.3, [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.43 (s, 9 H), 1.82 (m, 1 H), 1.97 (m, 1 H), 2.42 (dd, J1=16.3, J2=5.3 Hz, 1 H), 2.63 (dd, J1=16.5, J2=9.0 Hz, 1 H), 2.96 (m, 1 H), 3.50 (t, J=6.2 Hz, 2 H), 3.65 (s, 3 H), 4.48 (s, 2 H), 7.32 (m, 5 H).

Workup

  1. stirringstirring
  2. waitwas continuted for an additional 20 h
  3. filtrationThe mixture was filtered
  4. customthe filtrate partitioned between MTBE (1.5 L) and H2O (1.5 L)
  5. customThe aqueous phase was separated
  6. extractionback-extracted with MTBE (1.0 L)
  7. washThe combined organics were washed with H2O (2×1.5 L), brine (1 L)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated
  11. customto give a pale yellow oil

Sources & evidence

ORD record
ord-8bd37c731ed245dcbd6093e8700f3a05
Source dataset
uspto-grants-2015_07
Patent number
US09085581B2

Reaction notes

Loading…