Dimethyl Sulfoxide → (S)-2-tert-Butyl 7-methyl 3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2,7(1H)-dicarboxylate

HRID 339230Notes

Reaction equation

HRID 339230 reaction equation
[C@H:1]1([NH:11][C:12]([C@@H:14]2[CH2:23][C:22]3[C:17](=[CH:18][C:19](OS(C(F)(F)F)(=O)=O)=[CH:20][CH:21]=3)[CH2:16][N:15]2[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.CS(C)=O.CCN(CC)CC>CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CO>[C@H:1]1([NH:11][C:12]([C@@H:14]2[CH2:23][C:22]3[C:17](=[CH:18][C:19]([C:32]([O:34][CH3:35])=[O:33])=[CH:20][CH:21]=3)[CH2:16][N:15]2[C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 86705865(S)-tert-butyl 3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-7-(((trifluoromethyl)sulfonyl)oxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 86705864(S)-2-tert-Butyl 7-methyl 3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2,7(1H)-dicarboxylateYield 182.4%

Reagents, catalysts & solvents 3

HCID 812191,3-Bis(diphenylphosphino)propaneCatalystHCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A 20 mL scintillation vial with a septum top was charged sequentially with (S)-tert-butyl 3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-7-(((trifluoromethyl)sulfonyl)oxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate (1.39 g, 2.50 mmol), Pd(OAc)2 (0.028 g, 0.12 mmol), and 1,3-bis(diphenylphosphino)propane (0.052 g, 0.12 mmol). DMSO (3.7 mL), MeOH (2.5 mL), and Et3N (0.77 mL, 5.50 mmol) were then added, and the reaction mixture was stirred for 5 min. A CO balloon was then used to purge the reaction vial, turning the solution black. The reaction was topped with the CO balloon and heated to 70° C. for 12 h. The reaction mixture was then filtered through an ACRODISC®, and the filtrate was poured into a separatory funnel containing EtOAc and sat. aq. NH4Cl solution. The aqueous layer was extracted with EtOAc (2×). The combined organic layers were washed with sat. NaCl (2×), dried over MgSO4, filtered and concentrated in vacuo. The crude oil was purified by flash column chromatography (gradient elution from 0 to 50% EtOAc/hexanes) to afford the title compound (1.06 g, 2.28 mmol, 91%) as a light yellow solid. MS (ESI+) m/z 465.2 (M+H)+.

Workup

  1. customto purge the reaction vial,
  2. filtrationThe reaction mixture was then filtered through an ACRODISC®
  3. additionthe filtrate was poured into a separatory funnel
  4. additioncontaining EtOAc and sat. aq. NH4Cl solution
  5. extractionThe aqueous layer was extracted with EtOAc (2×)
  6. washThe combined organic layers were washed with sat. NaCl (2×)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude oil was purified by flash column chromatography (gradient elution from 0 to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e5c7533327264de7800dc5bf87e1968e
Source dataset
uspto-grants-2014_11
Patent number
US08889712B2

Reaction notes

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