Pyridine → (S)-tert-butyl 3-(acetamidomethyl)morpholine-4-carboxylate

HRID 1476313Notes

Reaction equation

HRID 1476313 reaction equation
[NH2:1][CH2:2][C@H:3]1[CH2:8][O:7][CH2:6][CH2:5][N:4]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].N1C=CC=CC=1.[C:22](Cl)(=[O:24])[CH3:23]>ClCCl.C(=O)(O)[O-].[Na+].[Cl-].[Na+]>[C:22]([NH:1][CH2:2][C@H:3]1[CH2:8][O:7][CH2:6][CH2:5][N:4]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])(=[O:24])[CH3:23]

Participants

7

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 44182324(S)-tert-Butyl 3-(aminomethyl)morpholine-4-carboxylate

Product 1

HCID 66723613(S)-tert-butyl 3-(acetamidomethyl)morpholine-4-carboxylate

Reagents, catalysts & solvents 3

HCID 5234Sodium ChlorideSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (S)-tert-butyl 3-(aminomethyl)morpholine-4-carboxylate (commercially available, 0.62 g, 2.87 mmol) in dichloromethane (28.0 ml) were added sequentially pyridine (0.5 ml, 5.73 mmol) and acetyl chloride (0.25 ml, 3.44 mmol). After 30 min the reaction was diluted with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The resulting mixture was extracted with ethyl acetate (×3), and the combined organic layers were then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting light yellow oil was purified by flash column chromatography (ISCO, SiO2, 0-10% methanol in ethyl acetate over 10 min) to afford (S)-tert-butyl 3-(acetamidomethyl)morpholine-4-carboxylate (0.741 g, yield: almost quantitative, INTERMEDIATE 86A STEP 1).

Workup

  1. extractionThe resulting mixture was extracted with ethyl acetate (×3)
  2. dry with materialthe combined organic layers were then dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting light yellow oil was purified by flash column chromatography (ISCO, SiO2, 0-10% methanol in ethyl acetate over 10 min)

Sources & evidence

ORD record
ord-4525b7bc618d412886101f76ffd6f8ed
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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