Diethyl Oxalate → HCID 71254945, compound

HRID 1508343Notes

Reaction equation

HRID 1508343 reaction equation
[Cl:1][C:2]1[C:3]([F:19])=[C:4]([C:8](=[O:18])[CH:9]([CH3:17])[C:10](=O)[C:11]([O:13]CC)=[O:12])[CH:5]=[CH:6][CH:7]=1.[Li+].C[Si]([N-:25][Si](C)(C)C)(C)C.C(OCC)(=O)C(OCC)=O>CCOCC>[Cl:1][C:2]1[C:3]([F:19])=[C:4]([C:8]2[O:18][N:25]=[C:10]([C:11]([OH:13])=[O:12])[C:9]=2[CH3:17])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 7268Diethyl OxalateHCID 2733832Lithium HexamethyldisilazideHCID 71254958HCID 71254958, compound

Product 1

HCID 71254945HCID 71254945, compoundYield 6%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

Ethyl 4-(3-chloro-2-fluorophenyl)-3-methyl-2,4-dioxobutanoate: To the solution of LiHMDS (1 M in THF) (3.19 mL, 3.19 mmol) in ether (12 mL) at −78° C. was added dropwise a solution of Intermediate 47B (0.59 g, 3.16 mmol) in ether (2 mL). After 45 min., diethyl oxalate (0.492 mL, 3.60 mmol) was added in one portion, and the reaction was warmed to rt. After 18 h, the reaction mixture was filtered, washing with ether. The filtrate was diluted with EtOAc, washed with 1 N HCl, brine, dried over Na2SO4, filtered and concentrated. Purification by silica gel chromatography yielded the desired product (0.057 g, 6%) as a yellow oil. MS(ESI) m/z: 241.0 (M-OEt)+. 1H NMR (500 MHz, CDCl3) δ 7.80 (ddd, J=8.0, 6.3, 1.7 Hz, 1H), 7.65 (ddd, J=7.8, 7.0, 1.9 Hz, 1H), 7.23 (td, J=8.0, 0.8 Hz, 1H), 4.91 (q, J=7.2 Hz, 1H), 4.31 (qd, J=7.2, 0.8 Hz, 2H), 1.46 (dd, J=7.2, 0.8 Hz, 3H), 1.34 (t, J=7.2 Hz, 3H) ppm.

Workup

  1. waitAfter 18 h
  2. filtrationthe reaction mixture was filtered
  3. washwashing with ether
  4. additionThe filtrate was diluted with EtOAc
  5. washwashed with 1 N HCl, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-d6f6666e12a8478caa15b8b63e510f7d
Source dataset
uspto-grants-2015_12
Patent number
US09221818B2

Reaction notes

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