Morpholine → 4-(3-Methoxy-5-nitrobenzoyl)morpholine

HRID 1914687Notes

Reaction equation

HRID 1914687 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([O:13][CH3:14])[CH:12]=1)[C:7]([OH:9])=O)([O-:3])=[O:2].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.[NH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>C1COCC1.C(Cl)Cl>[CH3:14][O:13][C:11]1[CH:10]=[C:6]([CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=1)[C:7]([N:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1)=[O:9]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 53002123-Methoxy-5-nitrobenzoic acid

Product 1

HCID 299083914-(3-Methoxy-5-nitrobenzoyl)morpholine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-nitro-5-methoxybenzoic acid (900 mg; 4.57 mmol; 1 eq; commercially available IMPAMEX) is dissolved in THF (5 mL) at room temperature. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.05 g; 5.48 mmol; 1.2 eq) and 1-hydroxybenzotriazole hydrate (987 mg; 7.3 mmol; 1.6 eq) are added in DCM (20 mL). The reaction mixture is stirred at room temperature for 25 min before adding morpholine (795.44 mg; 9.13 mmol; 2 eq). After 3 h, the reaction mixture is quenched with water and the organic phase recovered and washed with citric acid (5%). The aqueous phase is extracted with DCM. The organic phase is dried over MgSO4, and the solvent is evaporated under reduced pressure to afford 1.2 g (99%) as a yellow solid. The next step is carried out directly on the crude material. LC/MS: (ES+): 267.3; (ES−): 265.3.

Workup

  1. waitAfter 3 h
  2. customthe reaction mixture is quenched with water
  3. customthe organic phase recovered
  4. washwashed with citric acid (5%)
  5. extractionThe aqueous phase is extracted with DCM
  6. dry with materialThe organic phase is dried over MgSO4
  7. customthe solvent is evaporated under reduced pressure
  8. customto afford 1.2 g (99%) as a yellow solid

Sources & evidence

ORD record
ord-5a083985db42425e964aad1247059a22
Source dataset
uspto-grants-2013_12
Patent number
US08614215B2

Reaction notes

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