1,2-Dichloroethane → 2-(Morpholin-4-yl)acetamide

HRID 334936Notes

Reaction equation

HRID 334936 reaction equation
C(Cl)CCl.C1C=CC2N(O)N=[N:11]C=2C=1.[N:15]1([CH2:21][C:22]([OH:24])=O)[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.C(N(CC)CC)C>CN(C=O)C>[N:15]1([CH2:21][C:22]([NH2:11])=[O:24])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 111,2-Dichloroethane2×HCID 8471Triethylamine2×HCID 757711-Hydroxybenzotriazole2×HCID 4389684-Morpholineacetic acid2×

Product 1

HCID 6679102-(Morpholin-4-yl)acetamideYield 108.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of [5-(3-amino-ethoxy)-1,3-dihydro-isoindol-2-yl]-(2,4-dihydroxy-5-isopropyl-phenyl)-methanone hydrochloride (100 mg, 0.255 mmoles) in DMF (10 ml) was added EDC (59 mg, 0.306 mmoles), HOBt (41 mg, 0.306 mmoles), morpholin-4-yl-acetic acid (37 mg, 0.255 mmoles) and triethylamine (43 μl, 0.306 mmoles) and stirred at ambient temperature for one hour. To the reaction mixture was added further EDC (20 mg, 0.104 mmoles), HOBt (14 mg, 0.104 mmoles), morpholin-4-yl-acetic acid (12 mg, 0.083 mmoles) and triethylamine (14 μl, 0.100 mmoles) and stirred at ambient temperature for a further 2 hours. Solvent removed in vacuo. The residue was purified by flash chromatography [Biotage SP4: 25S, flow rate 25 ml/min, gradient 20% DMAW 90 in DCM to 100% DMAW 90] and then by preparative HPLC to give N-{2-[2,4-dihydroxy-5-isopropyl-benzoyl)-2,3-dihydro-1H-isoindol-5-yloxy]-ethyl}-2-morpholin-4-yl-acetamide as a colourless viscous oil (40 mg, 33%). 1H NMR (Me-d3-OD) 7.20 (1H, br s); 7.18 (1H, s); 6.90 (2H, br m); 6.40 (1H, s); 4.10 (2H, t); 3.73 (4H, m); 3.63 (2H, t); 3.20 (1H, m); 3.18 (2H, s); 2.60 (4H, m); 1.25 (6H, d). MS: [M+H]+ 484.

Workup

  1. stirringstirred at ambient temperature for a further 2 hours
  2. customSolvent removed in vacuo
  3. customThe residue was purified by flash chromatography [Biotage SP4: 25S, flow rate 25 ml/min, gradient 20% DMAW 90 in DCM to 100% DMAW 90]

Sources & evidence

ORD record
ord-d19c5f2f25764f9b9f545bc67bf0a229
Source dataset
uspto-grants-2014_11
Patent number
US08883790B2

Reaction notes

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