3,4-Dichlorobenzoic acid → tert-Butyl[(2S)-4-(3,4-dichlorobenzoyl)morpholin-2-yl]methylcarbamate

HRID 2211975Notes

Reaction equation

HRID 2211975 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([OH:7])=O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.[NH:43]1[CH2:48][CH2:47][O:46][C@@H:45]([CH2:49][NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[CH2:44]1>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([N:43]1[CH2:48][CH2:47][O:46][C@@H:45]([CH2:49][NH:50][C:51](=[O:57])[O:52][C:53]([CH3:55])([CH3:54])[CH3:56])[CH2:44]1)=[O:7]

Participants

7

Reactant 5

HCID 58173,4-Dichlorobenzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 42556135(R)-2-N-Boc-aminomethylmorpholine

Product 1

HCID 86760232tert-Butyl[(2S)-4-(3,4-dichlorobenzoyl)morpholin-2-yl]methylcarbamateYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of 3,4-dichlorobenzoic acid (0.5 g), 1-hydroxybenzotriazole (0.376 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.4329), and N,N-diisopropylethylamine (0.485 ml) in N,N-dimethylformamide (10 ml) was stirred at 20° C. for 10 min. The mixture was treated with tert-butyl (2R)-morpholin-2-ylmethylcarbamate (0.500 g, known compound WO 9639407A1) and stirred at 20° C. for 24 h. The mixture was partitioned between ethyl acetate (75 ml) and 2N aqueous hydrochloric acid (50 ml). The phases were separated and the organic extract washed with 2N aqueous hydrochloric acid (50 ml), saturated aqueous sodium hydrogen carbonate (2×50 ml), dried (MgSO4) and filtered. The solvent was removed in vacuo to give the title compound as a yellow oil, (0.774 g).

Workup

  1. stirringstirred at 20° C. for 24 h
  2. customThe mixture was partitioned between ethyl acetate (75 ml) and 2N aqueous hydrochloric acid (50 ml)
  3. customThe phases were separated
  4. extractionthe organic extract
  5. washwashed with 2N aqueous hydrochloric acid (50 ml), saturated aqueous sodium hydrogen carbonate (2×50 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-24eec11b523c4c5899e1ee063f0c5a7a
Source dataset
uspto-grants-2006_09
Patent number
US07101882B2

Reaction notes

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