Oxalyl chloride → 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)methyl)phenyl 4-(heptyloxy)benzoate

HRID 923533Notes

Reaction equation

HRID 923533 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[C:5]([C:13]([F:16])([F:15])[F:14])[CH:4]=1.C(Cl)(=O)C(Cl)=O.[CH2:23]([O:30][C:31]1[CH:64]=[CH:63][C:34]([C:35]([O:37][C:38]2[CH:43]=[CH:42][C:41]([CH2:44][N:45]([CH2:55][C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[C:46](=[O:54])[C:47]3[CH:52]=[CH:51][C:50]([NH2:53])=[CH:49][CH:48]=3)=[CH:40][CH:39]=2)=[O:36])=[CH:33][CH:32]=1)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>C(Cl)Cl.CN(C=O)C>[CH2:23]([O:30][C:31]1[CH:64]=[CH:63][C:34]([C:35]([O:37][C:38]2[CH:43]=[CH:42][C:41]([CH2:44][N:45]([CH2:55][C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[C:46](=[O:54])[C:47]3[CH:48]=[CH:49][C:50]([NH:53][C:10](=[O:12])[CH2:9][C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][C:5]=4[C:13]([F:16])([F:15])[F:14])=[CH:51][CH:52]=3)=[CH:40][CH:39]=2)=[O:36])=[CH:33][CH:32]=1)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 467375752-(4-Methoxy-2-(trifluoromethyl)phenyl)acetic acidHCID 892531254-((4-amino-N-(2-(tert-butoxy)-2-oxoethyl)benzamido)methyl)phenyl 4-(heptyloxy)benzoate

Product 1

HCID 892850004-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)methyl)phenyl 4-(heptyloxy)benzoateYield 58%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent3×

Procedure

Prepared using General Procedure 7: To 2-(4-methoxy-2-(trifluoromethyl)phenyl)acetic acid (299 mg, 1.28 mmol) in DCM (5 mL) and DMF (20 μL) was added oxalyl chloride (0.117 mL, 1.34 mmol). After stirring at room temperature for 30 min, 4-((4-amino-N-(2-(tert-butoxy)-2-oxoethyl)benzamido)methyl)phenyl 4-(heptyloxy)benzoate INT-4 (700 mg, 1.22 mmol) and TEA (0.424 mL, 3.05 mmol) in DCM (10 mL) were added. The reaction was stirred for 1 h then diluted with DCM (100 mL) and washed with NaHCO3 (100 mL). The crude product was purified by chromatography to provide 555 mg (58%) of 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)methyl)phenyl 4-(heptyloxy)benzoate INT-6. LCMS-ESI (m/z) calculated for C44H49F3N2O8: 791; no m/z observed, tR=3.28 min (Method 4).

Workup

  1. customPrepared
  2. stirringThe reaction was stirred for 1 h
  3. washwashed with NaHCO3 (100 mL)
  4. customThe crude product was purified by chromatography

Sources & evidence

ORD record
ord-afbecb4fa0c346ffb1279bc5650186cc
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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