Glycine, N,N-dimethyl-, ethyl ester → Tert-butyl 4-[2-(dimethylamino)-3-ethoxy-3-oxopropyl]benzoate

HRID 1919897Notes

Reaction equation

HRID 1919897 reaction equation
[CH3:1][N:2]([CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:3].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:21][C:22]1[CH:34]=[CH:33][C:25]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:24][CH:23]=1>C1COCC1>[CH3:1][N:2]([CH3:3])[CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:21][C:22]1[CH:34]=[CH:33][C:25]([C:26]([O:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[O:27])=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 118412Glycine, N,N-dimethyl-, ethyl esterHCID 2733832Lithium HexamethyldisilazideHCID 11414578Tert-butyl 4-(bromomethyl)benzoate

Product 1

HCID 57611943Tert-butyl 4-[2-(dimethylamino)-3-ethoxy-3-oxopropyl]benzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Ethyl (dimethylamino)acetate (0.16 mL, 1.11 mmol) was dissolved in THF (10 mL) and cooled to −78° C. LiHMDS (1.2 mL, 1M solution in THF) was added. The reaction was allowed to stir about 30 minutes. Tert-butyl 4-(bromomethyl)benzoate (0.3063 g, 1.13 mmol) in THF (3 mL) was slowly added to the reaction. The reaction was allowed to stir overnight under nitrogen, slowly warming to room temperature. The reaction was quenched with saturated ammonium chloride and diluted with ethyl acetate. The resulting mixture was separated. The aqueous layer was extracted three times with ethyl acetate. The combined organic layer was dried with sodium sulfate, filtered, and concentrated. The resulting residue was purified by column chromatography. 1H NMR 600 MHz (CDCl3) δ 7.87 (m, 2H), 7.24 (m, 2H), 4.08 (m, 1H), 4.06 (m, 1H), 3.41 (dd, 1H, J=9.2, 6.0), 3.07 (dd, 1H, J=13.5, 9.3), 2.97 (dd, 1H, J=13.4, 5.8), 2.39 (s, 6H), 1.56 (s, 9H), 1.16 (m, 3H). MS: cal'd 322 (MH+), exp 322 (MH+).

Workup

  1. stirringto stir overnight under nitrogen
  2. temperatureslowly warming to room temperature
  3. customThe reaction was quenched with saturated ammonium chloride
  4. additiondiluted with ethyl acetate
  5. customThe resulting mixture was separated
  6. extractionThe aqueous layer was extracted three times with ethyl acetate
  7. dry with materialThe combined organic layer was dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-6902794a871c4b74bc3a3dc3445db2b4
Source dataset
uspto-grants-2012_05
Patent number
US08168658B2

Reaction notes

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