Potassium Hydroxide → HCID 69818695, compound

HRID 1006367Notes

Reaction equation

HRID 1006367 reaction equation
[ClH:1].Cl.[CH:3]([C@H:16]1[N:21]2[CH2:22][CH2:23][CH2:24][C@H:20]2[CH2:19][N:18]([CH2:25][C:26]2[CH:31]=[C:30](Br)[CH:29]=[CH:28][C:27]=2[O:33][CH3:34])[CH2:17]1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(B(CC)[C:38]1[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=1)C.[OH-].[K+].C(=O)([O-])O.[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.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>[ClH:1].[ClH:1].[ClH:1].[CH:3]([C@H:16]1[N:21]2[CH2:22][CH2:23][CH2:24][C@H:20]2[CH2:19][N:18]([CH2:25][C:26]2[CH:31]=[C:30]([C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)[CH:29]=[CH:28][C:27]=2[O:33][CH3:34])[CH2:17]1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 4

HCID 14797Potassium HydroxideHCID 516892Sodium BicarbonateHCID 6428513-(Diethylboryl)pyridineHCID 69819834HCID 69819834, compound

Product 1

HCID 69818695HCID 69818695, compoundYield 73.2%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (4R,8aS)-4-benzhydryl-2-(5-bromo-2-methoxybenzyl)octahydropyrrolo[1,2-a]pyrazine dihydrochloride (100 mg), diethyl-3-pyridylboran (39.1 mg), tetrakis(triphenylphosphine)palladium (20.5 mg), powdered potassium hydroxide (29.8 mg) and tetrabutylammonium bromide (17.1 mg) in tetrahydrofuran (2 ml) were stirred for 8 hours at 70° C. After being cooled to room temperature, the reaction mixture was poured into aqueous saturated sodium hydrogen carbonate, and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The resulting residue was purified by preparative TLC (0.5 mm) with a mixture of dichloromethane and methanol (10:1) as an eluent. The resulting residue was treated with 4N hydrogen chloride in ethyl acetate to give (4R,8aS)-4-benzhydryl-2-[2-methoxy-5-(3-pyridyl)benzyl]octahydropyrrolo[1,2-a]pyrazine trihydrochloride (25.9 mg).

Workup

  1. temperatureAfter being cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe resulting residue was purified by preparative TLC (0.5 mm) with a mixture of dichloromethane and methanol (10:1) as an eluent
  7. additionThe resulting residue was treated with 4N hydrogen chloride in ethyl acetate

Sources & evidence

ORD record
ord-499a4cd5b5684312a56859ff2cbd929c
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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