Triethylamine → HCID 74788456, compound

HRID 406789Notes

Reaction equation

HRID 406789 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][CH2:8][C@@H:9]1[CH2:11][C@H:10]1[C:12]1[CH:17]=[C:16]([O:18]C)[CH:15]=[CH:14][C:13]=1[O:20]C)([CH3:4])([CH3:3])[CH3:2].B(Br)(Br)Br.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:22])[NH:7][CH2:8][C@@H:9]1[CH2:11][C@H:10]1[C:12]1[CH:17]=[C:16]([OH:18])[CH:15]=[CH:14][C:13]=1[OH:20])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 25134Boron tribromideHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 74891096HCID 74891096, compound

Product 1

HCID 74788456HCID 74788456, compoundYield 66.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of trans-[2-(2,5-dimethoxyphenyl)cyclopropylmethyl]carbamic acid tert-butyl ester (13) (4.20 g, 13.7 mmol) in CH2Cl2 (30 mL) at −78° C. was added BBr3 (1.0 M solution in CH2Cl2) (47.8 mL, 47.8 mmol) dropwise. The solution was warmed to rt, and the reaction mixture was quenched with MeOH (110 mL) and concentrated in vacuo. This process was repeated until no white fumes were observed upon addition of MeOH to give a crude product as pale yellow oils. The crude product was used without any further purification. A solution of the crude product, Boc2O (3.28 g, 15.0 mmol), and triethylamine (7.62 mL, 54.7 mmol) in CH2Cl2 (30 mL) was stirred at rt for 30 min. To the resulting mixture were added sat. aq NaHCO3, and the aqueous layer was extracted with CH2Cl2 (×2). The organic layer was further washed with water (×1), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography using gradient elution from 0% EtOAc-hexane to 30% EtOAc-hexane to afford the title compounds as a pale yellow oil (2.55 g, 66.8% yield). 1H NMR (400 MHz, CDCl3) δ 6.73 (d, J=8.4 Hz, 1 H), 6.57 (dd, J=8.8 Hz, J=2.6 Hz, 1 H), 6.42 (d, J=2.6 Hz, 1 H), 5.01 (bs, 1 H), 4.45 (s, 1 H), 3.51-3.44 (m, 1 H), 2.92-2.85 (m, 1 H), 1.89-1.87 (m, 1 H), 1.47 (s, 9 H), 1.06-1.01 (m, 1 H), 0.92-0.90 (m, 1 H), 0.75-0.72 (m, 1 H).

Workup

  1. customthe reaction mixture was quenched with MeOH (110 mL)
  2. concentrationconcentrated in vacuo
  3. additionwere observed upon addition of MeOH
  4. customto give a crude product as pale yellow oils
  5. customThe crude product was used without any further purification
  6. extractionthe aqueous layer was extracted with CH2Cl2 (×2)
  7. washThe organic layer was further washed with water (×1)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography
  12. washelution from 0% EtOAc-hexane to 30% EtOAc-hexane

Sources & evidence

ORD record
ord-b6a835cc4ca64ff789809b9a547f78e1
Source dataset
uspto-grants-2014_06
Patent number
US08754132B2

Reaction notes

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