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 1793523Notes

Reaction equation

HRID 1793523 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) δ 7.20 (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-9e135e9c0edb4f25b9b636576e3b6856
Source dataset
uspto-grants-2006_07
Patent number
US07081455B2

Reaction notes

Loading…