Tert-butyl (6aS,10aR)-2-bromo-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)carboxylate → tert-butyl (6aS,10aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylate

HRID 1266075Notes

Reaction equation

HRID 1266075 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8]3=[C:9]([CH2:11][CH2:12][N:7]3[C@H:6]3[CH2:13][CH2:14][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][C@@H:5]23)[CH:10]=1.[CH2:24]([O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[C:29]([C:36]([F:39])([F:38])[F:37])[CH:28]=1)[CH3:25]>COCCOC.O.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>[CH2:24]([O:26][C:27]1[CH:32]=[CH:31][C:30]([C:2]2[CH:3]=[C:4]3[C:8]4=[C:9]([CH2:11][CH2:12][N:7]4[C@H:6]4[CH2:13][CH2:14][N:15]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH2:16][C@@H:5]34)[CH:10]=2)=[C:29]([C:36]([F:37])([F:38])[F:39])[CH:28]=1)[CH3:25]

Participants

6

Reactant 2

HCID 20577007Tert-butyl (6aS,10aR)-2-bromo-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)carboxylateHCID 220216774-Ethoxy-2-(trifluoromethyl)phenylboronic acid

Product 1

HCID 10435595tert-butyl (6aS,10aR)-2-[4-ethoxy-2-(trifluoromethyl)phenyl]4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH)-carboxylateYield 57.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Tert-butyl (6aS,10aR)-2-bromo-4,5,7,8,10,10a-hexahydropyrido[4,3-b]pyrrolo[3,2,1-hi]indole-9(6aH) carboxylate (189 mg, 0.5 mmol) was dissolved in DME (7.8 mL). Ba(OH)2 8H2O (236.6 mg, 0.75 mmol) in H2O (2.6 mL) was added. 4-ethoxy-2-trifluoromethylphenyl boronic acid (140 mg, 0.6 mmol) was added followed by Pd(PPh3)4 (12 mg, 0.01 mmol). The reaction flask was degassed and refluxed under a nitrogen atmosphere for 18 hrs. After cooling to RT, the reaction was concentrated in vacuo. Water (10 mL) and EtOAc (10 mL) were added. The layers were separated and the aqueous phase was extracted with EtOAc (2×10 mL). The combined organic layer was washed with brine (2×10 mL), dried over MgSO4 and concentrated in vacuo and after chromatographic purification (30% EtOAc/Hexane) to afford the title compound (140 mg, 57%). 1H NMR (CDCl3, 300 MHz) δ7.20 (d, 2H, J=5.9 Hz), 7.19 (s, 1H), 7.01 (dd, 1H, J=6.2, 2.2 Hz), 6.85 (s, 1H), 6.81 (s, 1H), 4.05-4.10 (m, 3H), 3.82-3.94 (m, 1H), 3.64-3.68 (m, 1H), 3.22-3.44 (m, 4H), 2.84-3.10 (m, 3H), 1.80-1.90 (m, 2H), 1.42-1.47 (m, 12H) ppm. MS-ApCI: 489 [M+H+].

Workup

  1. customThe reaction flask was degassed
  2. temperaturerefluxed under a nitrogen atmosphere for 18 hrs
  3. concentrationthe reaction was concentrated in vacuo
  4. additionWater (10 mL) and EtOAc (10 mL) were added
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted with EtOAc (2×10 mL)
  7. washThe combined organic layer was washed with brine (2×10 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customafter chromatographic purification (30% EtOAc/Hexane)

Sources & evidence

ORD record
ord-71f940dd10b34ae2afca7b33e83a2981
Source dataset
uspto-grants-2003_04
Patent number
US06548493B1

Reaction notes

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