Benzoyl chloride → (S)-2-{[(3S,8S)-7-Benzoyl-3-(4-cyclohexylmethoxy-phenyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yloxy)-phenyl]-propionic acid

HRID 879863Notes

Reaction equation

HRID 879863 reaction equation
Cl.Cl.C[O:4][C:5](=[O:54])[C@@H:6]([NH:23][C:24]([C@@H:26]1[CH2:35][C:34]2[CH:33]=[C:32]3[O:36][CH2:37][C@H:38]([C:40]4[CH:45]=[CH:44][C:43]([O:46][CH2:47][CH:48]5[CH2:53][CH2:52][CH2:51][CH2:50][CH2:49]5)=[CH:42][CH:41]=4)[O:39][C:31]3=[CH:30][C:29]=2[CH2:28][NH:27]1)=[O:25])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]([CH3:21])[C:16]=2[CH3:22])=[CH:10][CH:9]=1.[C:55](Cl)(=[O:62])[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1>CCOC(C)=O.C([O-])(O)=O.[Na+]>[C:55]([N:27]1[C@H:26]([C:24]([NH:23][C@@H:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([CH3:21])[C:16]=3[CH3:22])=[CH:10][CH:9]=2)[C:5]([OH:54])=[O:4])=[O:25])[CH2:35][C:34]2[CH:33]=[C:32]3[O:36][CH2:37][C@H:38]([C:40]4[CH:45]=[CH:44][C:43]([O:46][CH2:47][CH:48]5[CH2:49][CH2:50][CH2:51][CH2:52][CH2:53]5)=[CH:42][CH:41]=4)[O:39][C:31]3=[CH:30][C:29]=2[CH2:28]1)(=[O:62])[C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1

Participants

5

Reactant 2

HCID 7412Benzoyl chlorideHCID 66719304(S)-2-{[(3S,8S)-3-(4-Cyclohexylmethoxy-phenyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yloxy)-phenyl]-propionic acid methyl ester di-hydrochloride

Product 1

HCID 58327232(S)-2-{[(3S,8S)-7-Benzoyl-3-(4-cyclohexylmethoxy-phenyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yloxy)-phenyl]-propionic acid

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

(S)-2-{[(3S,8S)-3-(4-Cyclohexylmethoxy-phenyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yloxy)-phenyl]-propionic acid methyl ester dihydrochloride (19 mg) was dissolved in 1:1 EtOAc and saturated aqueous NaHCO3 and benzoyl chloride (3 eq.) added. After stirring at room temperature for 1 hour, the layers were separated and the organic layer was dried over Na2SO4 and evaporated. The residue was purified over silica (hexanes to 8:2 hexanes-EtOAc to 6:4 hexanes-EtOAc to 6:4 hexanes-EtOAc+2% MeOH to DCM+3% MeOH). The resulting compound was hydrolyzed according to General Procedure B to give the title compound (20 mg). LCMS (m/z): 797.

Workup

  1. additionadded
  2. customthe layers were separated
  3. dry with materialthe organic layer was dried over Na2SO4
  4. customevaporated
  5. customThe residue was purified over silica (hexanes to 8:2 hexanes-EtOAc to 6:4 hexanes-EtOAc to 6:4 hexanes-EtOAc+2% MeOH to DCM+3% MeOH)

Sources & evidence

ORD record
ord-2497fb323a6b465582b321fecce76f15
Source dataset
uspto-grants-2015_03
Patent number
US08987295B2

Reaction notes

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