Formaldehyde → (S)-2-Chloro-11-[3-(2-methoxy-ethyl)-4-methyl-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine dihydrochloride

HRID 131433Notes

Reaction equation

HRID 131433 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:5]2[NH:6][C:7]3[CH:24]=[CH:23][CH:22]=[CH:21][C:8]=3[N:9]=[C:10]([N:11]3[CH2:16][CH2:15][NH:14][C@@H:13]([CH2:17][CH2:18][O:19][CH3:20])[CH2:12]3)[C:4]=2[CH:3]=1.C=O.[C:29](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl>[ClH:1].[ClH:1].[Cl:1][C:2]1[CH:26]=[CH:25][C:5]2[NH:6][C:7]3[CH:24]=[CH:23][CH:22]=[CH:21][C:8]=3[N:9]=[C:10]([N:11]3[CH2:16][CH2:15][N:14]([CH3:29])[C@@H:13]([CH2:17][CH2:18][O:19][CH3:20])[CH2:12]3)[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 10022095(S)-2-Chloro-11-[3-(2-methoxy-ethyl)-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine

Product 1

HCID 69210007(S)-2-Chloro-11-[3-(2-methoxy-ethyl)-4-methyl-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine dihydrochlorideYield 252.8%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Combine (S)-2-chloro-11-[3-(2-methoxy-ethyl)-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine (0.474 g, 1.27 mmol) and 37% formaldehyde solution (0.1 mL, 1.34 mmol) in 1,2-dichloroethane (20 mL). Stir for 10 minutes and add sodium triacetoxy borohydride (0.542 g, 2.55 mmol). Stir an additional 30 minutes and then pour solution onto saturated sodium bicarbonate solution. Extract with methylene chloride to give 0.555 g of the crude product. Silica gel chromatography, eluting with methylene chloride:methanol (100:5), gives 0.490 g of the title compound as the free base. The dihydrochloride salt precipitates in ethyl acetate as a solid: mp 205° C.; mass spectrum (ion spray): m/z=385 (M+1).

Workup

  1. stirringStir an additional 30 minutes
  2. extractionExtract with methylene chloride
  3. customto give 0.555 g of the crude product
  4. washSilica gel chromatography, eluting with methylene chloride:methanol (100:5)

Sources & evidence

ORD record
ord-1c05e453bb974a55aaa7ec7fb3612e5d
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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