Sodium Carbonate → (S)-tert-Butyl 7-((S)-1-((benzyloxy)carbonyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-2,5-dihydro-1H-pyrrol-3-yl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 339247Notes

Reaction equation

HRID 339247 reaction equation
[C@H:1]1([NH:11][C:12]([C@@H:14]2[CH:18]=[C:17](OS(C(F)(F)F)(=O)=O)[CH2:16]N2C(OCC2C=CC=CC=2)=O)=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[C@H:37]1([NH:47][C:48]([C@@H:50]2[CH2:59][C:58]3[C:53](=[CH:54][C:55](B4OC(C)(C)C(C)(C)O4)=[CH:56][CH:57]=3)[CH2:52][N:51]2[C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])=[O:49])[C:46]2[C:41](=CC=CC=2)[CH2:40][CH2:39][CH2:38]1.[C:76]([O-:79])([O-])=[O:77].[Na+].[Na+].[NH4+:82].[Cl-]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:6]([O:79][C:76]([N:82]1[C@H:14]([C:12](=[O:13])[NH:11][C@H:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:4][CH2:3][CH2:2]2)[CH:18]=[C:17]([C:57]2[CH:58]=[C:53]3[C:54]([CH2:59][C@@H:50]([C:48](=[O:49])[NH:47][C@H:37]4[C:46]5[C:41](=[CH:17][CH:18]=[CH:14][CH:12]=5)[CH2:40][CH2:39][CH2:38]4)[N:51]([C:69]([O:71][C:72]([CH3:73])([CH3:74])[CH3:75])=[O:70])[CH2:52]3)=[CH:55][CH:56]=2)[CH2:16]1)=[O:77])[C:5]1[CH:4]=[CH:3][CH:2]=[CH:1][CH:10]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 86705883(S)-benzyl 2-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-4-(((trifluoromethyl)sulfonyl)oxy)-2,5-dihydro-1H-pyrrole-1-carboxylateHCID 86705884(S)-tert-butyl 3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 86705882(S)-tert-Butyl 7-((S)-1-((benzyloxy)carbonyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-2,5-dihydro-1H-pyrrol-3-yl)-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 79%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of (S)-benzyl 2-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-4-(((trifluoromethyl)sulfonyl)oxy)-2,5-dihydro-1H-pyrrole-1-carboxylate (226 mg, 0.43 mmol), (S)-tert-butyl 3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (229 mg, 0.43 mmol) and 2M aq. Na2CO3 (540 μL, 1.08 mmol) in dioxane (4.3 mL) was degassed with argon. Pd(Ph3P)4 (50 mg, 0.043 mmol) was added, and the reaction mixture was stirred at 100° C. for 2 h and then poured into a sep funnel containing sat. NH4Cl. The aqueous layer was extracted with EtOAc (3×). The combined organic extracts were washed with sat. NaCl, dried over Na2SO4, filtered and concentrated in vacuo to give a crude oil. Purification using flash column chromatography (gradient elution from 0 to 100% EtOAc/hexanes) provided the title compound (265 mg, 79%) as a colorless oil. MS (ESI+) m/z 781.2 (M+H)+.

Workup

  1. additionpoured into a sep funnel
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. washThe combined organic extracts were washed with sat. NaCl
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a crude oil
  8. customPurification
  9. washflash column chromatography (gradient elution from 0 to 100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-40c8a3bd285e488eb04936b416bb2318
Source dataset
uspto-grants-2014_11
Patent number
US08889712B2

Reaction notes

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