Phenylboronic Acid → (3S,8S)-3-(4-phenoxy-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

HRID 391990Notes

Reaction equation

HRID 391990 reaction equation
[CH3:1][O:2][C:3]([CH: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]([OH:25])=[CH:21][CH:20]=4)[O:18][C:10]3=[CH:9][C:8]=2[CH2:7][N:6]1[C@H:26]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:27][CH3:28])=[O:4].[C:35]1(B(O)O)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Cu+2]>[CH3:1][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][C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)=[CH:21][CH:20]=4)[O:18][C:10]3=[CH:9][C:8]=2[CH2:7][N:6]1[C@H:26]([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[CH2:27][CH3:28])=[O:4]

Participants

5

Reactant 2

HCID 66827Phenylboronic AcidHCID 66719659(S)-3-(4-Hydroxy-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 66719814(3S,8S)-3-(4-phenoxy-phenyl)-7-((S)-1-phenyl-propyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carboxylic acid methyl esterYield 62.9%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

(S)-3-(4-Hydroxy-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 (30 mg), Cu(OAc)2, (25 mg), phenyl boronic acid (32 mg) and molecular sieves suspended in 5 mL DCM. TEA (0.064 mL) added, reaction flushed with oxygen and stirred at room temperature for 20 hours. The resulting mixture poured onto EtOAc and 10% sodium carbonate. Organic layer washed 3 times with 10% sodium carbonate, dried over sodium sulfate and concentrated. Residue purified over silica (hexanes to 9:1 hexanes/EtOAc) to give (3S,8S)-3-(4-phenoxy-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 (22 mg). LCMS (m/z): 537.

Workup

  1. customreaction
  2. customflushed with oxygen
  3. additionThe resulting mixture poured onto EtOAc and 10% sodium carbonate
  4. washOrganic layer washed 3 times with 10% sodium carbonate
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customResidue purified over silica (hexanes to 9:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-8f0b0450d8ad4b2ba729d041ffe0f4d0
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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