Acetic Acid → Eicosa-5,8,11,14-tetraenoic acid (4-chloro-benzyl)-(2,4-dichloro-phenyl)amide

HRID 392605

Reaction equation

HRID 392605 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[Cl:10][C:11]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:12]=1[NH2:13].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[C:37](O)(=[O:57])[CH2:38][CH2:39][CH2:40]/[CH:41]=[CH:42]\[CH2:43]/[CH:44]=[CH:45]\[CH2:46]/[CH:47]=[CH:48]\[CH2:49]/[CH:50]=[CH:51]\[CH2:52][CH2:53][CH2:54][CH2:55][CH3:56].C(Cl)(=O)C(Cl)=O>C(Cl)Cl.CN(C=O)C.ClCCCl>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:13]([C:12]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:11]=2[Cl:10])[C:37](=[O:57])[CH2:38][CH2:39][CH2:40][CH:41]=[CH:42][CH2:43][CH:44]=[CH:45][CH2:46][CH:47]=[CH:48][CH2:49][CH:50]=[CH:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])=[CH:4][CH:3]=1

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 77264-ChlorobenzaldehydeHCID 111232,4-DichloroanilineHCID 65578Oxalyl chlorideHCID 444899Arachidonic AcidHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 73022406Eicosa-5,8,11,14-tetraenoic acid (4-chloro-benzyl)-(2,4-dichloro-phenyl)amideYield 91%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent3×

Procedure

Used the same procedure as above to synthesize 1.15 g (56%) of the desired amine from 4-chlorobenzaldehyde (1.0 g, 7.11 mmol), 2,4-dichloroaniline (1.27 g, 7.83 mmol), sodium triacetoxyborohydride (2.41 g, 11.38 mmol), acetic acid (0.41 mL, 7.11 mmol) and 1,2-dichloroethane (32 mL). 1H NMR δ4.36 (d, 2H, 5.8 Hz), 4.73 (br.s, 1H), 6.46 (d, 1H, 8.5 Hz), 7.03 (dd, 1H, 8.7, 2.2 Hz), 7.22-7.34 (m, 5H). Used the same procedure as above for generating the acid chloride and the subsequent condensation product: used arachidonic acid (234 mg, 0.77 mmol) in CH2Cl2 (5 mL) with oxalyl chloride (147 μL, 1.69 mmol) and DMF (2 drops). The acid chloride in CH2Cl2 (3 mL) was subsequently added to the respective amine (1.1 g, 3.84 mmol) in CH2Cl2 (5 mL). Isolated the desired product (O-2248; 400 mg, 91%) after purification by column chromatography (hexanes/EtOAc 97%/3% then 95%/5%) as a single rotomer. 1H NMR δ0.88 (t, 3H, 6.9 Hz), 1.24-1.41 (m, 6H), 1.67 (q, 2H, 7.1 Hz), 1.94 -2.05 (m, 6H), 2.75 (m, 6H), 4.03 (d, 1H, 14.3 Hz), 5.22-5.40 (m, 8H), 5.48 (d, 1H, 14.3 Hz), 6.70 (d, 1H, 8.5 Hz), 7.10-7.28 (m, 5H), 7.52 (d, 1H, 2.2 Hz). Anal. Calcd for C33H40NOCl3: C, 69.33; H, 7.06. Found: C, 69.17; H, 7.20.

Sources & evidence

ORD record
ord-1d24f0ebcd6746e7a155adb22639a804
Source dataset
uspto-grants-2004_10
Patent number
US06800770B2

Linked notes

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