Sodium triacetoxyborohydride → (4R,8aS)-4-benzhydryl-2-(2-chloro-6-methoxybenzyl)octahydropyrrolo[1,2-a]pyrazine

HRID 1006365Notes

Reaction equation

HRID 1006365 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:15][C:16]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:17]=1[CH:18]=O.Cl.Cl.[CH:28]([C@H:41]1[N:46]2[CH2:47][CH2:48][CH2:49][C@H:45]2[CH2:44][NH:43][CH2:42]1)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CN(C)C=O>[CH:28]([C@H:41]1[N:46]2[CH2:47][CH2:48][CH2:49][C@H:45]2[CH2:44][N:43]([CH2:18][C:17]2[C:20]([O:24][CH3:25])=[CH:21][CH:22]=[CH:23][C:16]=2[Cl:15])[CH2:42]1)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 109649712-Chloro-6-methoxybenzaldehydeHCID 69819474(4R,8aS)-4-benzhydryloctahydropyrrolo[1,2-a]pyrazine dihydrochloride

Product 1

HCID 69819868(4R,8aS)-4-benzhydryl-2-(2-chloro-6-methoxybenzyl)octahydropyrrolo[1,2-a]pyrazineYield 49.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A 1M solution of sodium triacetoxyborohydride in N,N-dimethylformamide (75 μl) was added portionwise to a mixture of 2-chloro-6-methoxybenzaldehyde (9.4 mg) and a solution of (4R,8aS)-4-benzhydryloctahydropyrrolo[1,2-a]pyrazine dihydrochloride (18.3 mg) in N,N-dimethylformamide (50 μl) at 25° C. and the whole was stirred at room temperature for 2 hours. The mixture was purified by high pressure liquid chromatography eluting with aqueous 0.1% trifluoroacetic acid solution-acetonitrile (90:10→10:90). The solution was concentrated in vacuo. To the residue was added ethyl acetate and aqueous 5% potassium carbonate solution. The mixture was applied on liquid/liquid extraction cartridge (CE1000M, VARIAN) and eluted with ethyl acetate. The eluate was concentrated in vacuo to give (4R,8aS)-4-benzhydryl-2-(2-chloro-6-methoxybenzyl)octahydropyrrolo[1,2-a]pyrazine (11.0 mg)

Workup

  1. customThe mixture was purified by high pressure liquid chromatography
  2. washeluting with aqueous 0.1% trifluoroacetic acid solution-acetonitrile (90:10→10:90)
  3. concentrationThe solution was concentrated in vacuo
  4. additionTo the residue was added ethyl acetate and aqueous 5% potassium carbonate solution
  5. extractionThe mixture was applied on liquid/liquid extraction cartridge (CE1000M, VARIAN)
  6. washeluted with ethyl acetate
  7. concentrationThe eluate was concentrated in vacuo

Sources & evidence

ORD record
ord-ce56781e7a61467a9ac6f22706a1b605
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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