Hydrochloric Acid → (3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid

HRID 391847Notes

Reaction equation

HRID 391847 reaction equation
C[O:2][C:3]([C@@H:5]1[CH2:14][C:13]2[CH:12]=[C:11]3[O:15][CH2:16][C@@H:17]([C:19]4[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]5[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([Cl:34])[CH:28]=5)=[CH:21][CH:20]=4)[O:18][C:10]3=[CH:9][C:8]=2[CH2:7][N:6]1[C@H:35]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:36][CH3:37])=[O:4].[OH-].[K+].Cl.CCOC(C)=O>C1COCC1.CO.[Cl-].[Na+].O>[Cl:34][C:29]1[CH:28]=[C:27]([CH:32]=[CH:31][C:30]=1[Cl:33])[CH2:26][O:25][C:22]1[CH:21]=[CH:20][C:19]([C@@H:17]2[CH2:16][O:15][C:11]3=[CH:12][C:13]4[CH2:14][C@@H:5]([C:3]([OH:4])=[O:2])[N:6]([C@H:35]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)[CH2:36][CH3:37])[CH2:7][C:8]=4[CH:9]=[C:10]3[O:18]2)=[CH:24][CH:23]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 14797Potassium HydroxideHCID 58327464(3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid methyl ester

Product 1

HCID 58327155(3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acidYield 55%

Reagents, catalysts & solvents 2

HCID 21899815MeOH tetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

(3R,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid methyl ester (934 mg) was dissolved in 120 mL of THF-MeOH (1-4) and 9 mL KOH was added over 1 hour. The resulting mixture stirred at room temperature for 4 days. The pH was adjusted to about 7 with 1 N HCl and brine and EtOAc added. The organic solution was dried over Na2SO4 and evaporated. The residue was purified by silica gel flash chromatography (DCM-MeOH 99.5:0.5 to DCM-MeOH 95:5) to give 0.502 g of product after drying. LCMS: m/z 605.

Workup

  1. additionadded
  2. dry with materialThe organic solution was dried over Na2SO4
  3. customevaporated
  4. customThe residue was purified by silica gel flash chromatography (DCM-MeOH 99.5:0.5 to DCM-MeOH 95:5)

Sources & evidence

ORD record
ord-dd11e39d10164b019f2f11326bb1af6a
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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