Oxalyl chloride → Ethyl 6-chloro-7-(4-(1-(4-chlorophenyl)-3-hydroxypropan-2-ylcarbamoyl)phenoxy)chroman-4-carboxylate

HRID 1021534Notes

Reaction equation

HRID 1021534 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23].C(Cl)(=O)C(Cl)=O.C(N(C(C)C)C(C)C)C.[NH2:42][CH:43]([CH2:46][C:47]1[CH:52]=[CH:51][C:50]([Cl:53])=[CH:49][CH:48]=1)[CH2:44][OH:45]>ClCCl.CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:14]=[CH:15][C:16]([C:17](=[O:19])[NH:42][CH:43]([CH2:44][OH:45])[CH2:46][C:47]3[CH:52]=[CH:51][C:50]([Cl:53])=[CH:49][CH:48]=3)=[CH:20][CH:21]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 548289beta-Amino-4-chlorobenzenepropanolHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid

Product 1

HCID 67167139Ethyl 6-chloro-7-(4-(1-(4-chlorophenyl)-3-hydroxypropan-2-ylcarbamoyl)phenoxy)chroman-4-carboxylateYield 76.82%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (0.100 g, 0.2654 mmol) in dichloromethane (1.5 ml) and DMF (1 drop) was added oxalyl dichloride (0.02778 ml, 0.3185 mmol), and the reaction was stirred for 30 minutes. N-ethyl-N-isopropylpropan-2-amine (0.1112 ml, 0.6370 mmol) and 2-amino-3-(4-chlorophenyl)propan-1-ol (0.06405 g, 0.3450 mmol) were added, and the reaction was stirred for 16 hours. The reaction was diluted with EtOAc and washed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified on a Biotage SP1 system eluting with 25-100% EtOAc in hexanes to yield 111 mg of the title compound (76.82% yield).

Workup

  1. stirringthe reaction was stirred for 16 hours
  2. washwashed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified on a Biotage SP1 system
  7. washeluting with 25-100% EtOAc in hexanes

Sources & evidence

ORD record
ord-3250da268497440e90519283666f87d1
Source dataset
uspto-grants-2014_05
Patent number
US08716498B2

Reaction notes

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