Calcium Chloride → HCID 402597, compound

HRID 1374537Notes

Reaction equation

HRID 1374537 reaction equation
[Cl-].[Ca+2].[Cl-].Br[C:5]1[C:15]2[CH2:14][NH:13][CH2:12][CH2:11][C:10]34[CH:21]=[CH:20][C@H:19]([OH:22])[CH2:18][CH:16]3[O:17][C:8]([C:9]=24)=[C:7]([O:23][CH3:24])[CH:6]=1>[Zn]>[CH3:24][O:23][C:7]1[CH:6]=[CH:5][C:15]2[CH2:14][NH:13][CH2:12][CH2:11][C:10]34[CH:21]=[CH:20][C@H:19]([OH:22])[CH2:18][CH:16]3[O:17][C:8]=1[C:9]=24

Participants

4

Reactant 2

HCID 5284359Calcium ChlorideHCID 9928418HCID 9928418, compound

Product 1

HCID 402597HCID 402597, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 23994ZincCatalyst

Procedure

Activated zinc (89.0 g, 1.36 mol) and calcium chloride (44.0 g, 0.40 mol) were added to a solution of (6R)-1-bromo-3-methoxy-5,6,9,10,11,12-hexahydro-4aH-[1]benzofuro[3a,3,2-ef][2]benzazepin-6-ol (3) (20.0 g, 56.8 mmol) in 50% EtOX (1000 ml). The reaction mixture was refluxed for 18 hours and filtered on Celite. The filtrate was concentrated by evaporation, the residue was diluted with 2N hydrochloric acid (500 ml) and extracted with EtOAc (3×400 ml). The pH of the aqueous phase was set at above 8.5 with concentrated ammonia and extracted with CH2Cl2 (3×100 ml) and with CH2Cl2:MeOH=9:1 (3×100 ml). The combined organic extracts were washed with brine (200 ml), dried (Na2SO4) and concentrated by evaporation to produce 12.3 g (79.0% of compound 4: 1H-NMR (CDCl3) δ 6.62 (b, 2H), 6.02 (m, 2H), 4.61 (b, 1H), 4.14 (t, J=4.3 Hz, 1H), 3.98 (d, J=5.0 Hz, 2H), 3.83 (s, 3H), 3.30 (m, 1H), 2.69 (t, J=15.7, 1H), 2.10–1.63 (m, 4H); 13C-NMR (CDCl3) δ 146.2 (s), 144.1 (s), 133.1 (s), 131.7 (s), 127.8 (d), 126.8 (d), 120.8 (d), 111.1 (d), 88.4 (d), 61.9 (d), 55.9 (q), 53.3 (t), 48.5 (s), 46.7 (t), 39.4 (t), 29.9 (t). Anal. (C20H26N2O4) C, H, N.

Workup

  1. temperatureThe reaction mixture was refluxed for 18 hours
  2. filtrationfiltered on Celite
  3. concentrationThe filtrate was concentrated by evaporation
  4. additionthe residue was diluted with 2N hydrochloric acid (500 ml)
  5. extractionextracted with EtOAc (3×400 ml)
  6. extractionextracted with CH2Cl2 (3×100 ml) and with CH2Cl2
  7. washThe combined organic extracts were washed with brine (200 ml)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-6474998571a34ad6a29afb2f1858cc1b
Source dataset
uspto-grants-2007_01
Patent number
US07166588B2

Reaction notes

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