1,2-Dichloroethane → N-{(1R,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-pentanoylbenzamide

HRID 1783252Notes

Reaction equation

HRID 1783252 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11](=[O:16])[CH2:12][CH2:13][CH2:14][CH3:15])[CH:10]=1)[C:5]([OH:7])=O.FC(F)(F)C(O)=O.[NH2:24][C@@H:25]([CH2:39][C:40]1[CH:45]=[C:44]([F:46])[CH:43]=[C:42]([F:47])[CH:41]=1)[C@H:26]([OH:38])[CH2:27][NH:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH3:37])[CH:31]=1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>C(Cl)Cl>[F:46][C:44]1[CH:45]=[C:40]([CH:41]=[C:42]([F:47])[CH:43]=1)[CH2:39][C@@H:25]([NH:24][C:5](=[O:7])[C:4]1[CH:8]=[C:9]([C:11](=[O:16])[CH2:12][CH2:13][CH2:14][CH3:15])[CH:10]=[C:2]([CH3:1])[CH:3]=1)[C@H:26]([OH:38])[CH2:27][NH:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH3:37])[CH:31]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 210858393-Methyl-5-pentanoylbenzoic acidHCID 69869154(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol Trifluoroacetate

Product 1

HCID 21086265N-{(1R,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-3-methyl-5-pentanoylbenzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-methyl-5-pentanoylbenzoic acid (IX-LXXVII, 112 mg, 0.589 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-methoxybenzyl)amino]-2-butanol dihydrochloride (VIII, 239 mg, 0.589 mmol), HOBt (80 mg, 0.589 mmol), and N-methylmorpholine (250 mg, 2.47 mmol) in methylene chloride (3 mL) is added EDC (203 mg, 1.06 mmol). The reaction mixture is stirred overnight and then partitioned between ethyl acetate and water. The organic phase is washed with hydrochloric acid (1 N), saturated sodium bicarbonate, saline, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica; methylene chloride/methanol, 12/1) gives the title compound, IR (ATR): 3297, 2957, 1687 and 1628 cm−1; APCI-MS (m/z) [M+H]+=539.

Workup

  1. custompartitioned between ethyl acetate and water
  2. washThe organic phase is washed with hydrochloric acid (1 N), saturated sodium bicarbonate, saline
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash column chromatography (silica; methylene chloride/methanol, 12/1)

Sources & evidence

ORD record
ord-8237904813f545a79abe0272158bcf6a
Source dataset
uspto-grants-2009_03
Patent number
US07498436B2

Reaction notes

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