Formaldehyde → HCID 135539058, compound

HRID 131431Notes

Reaction equation

HRID 131431 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:15][C:9]=3[C:8]([N:20]3[CH2:25][CH2:24][NH:23][C@@H:22]([CH2:26][CH2:27][CH2:28][O:29][CH3:30])[CH2:21]3)=[N:7][C:6]=2[CH:31]=1.C=O.[C:34](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.C(=O)(O)[O-].[Na+]>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10]3[CH:12]=[CH:13][C:14]([C:16]([F:19])([F:17])[F:18])=[CH:15][C:9]=3[C:8]([N:20]3[CH2:25][CH2:24][N:23]([CH3:34])[C@@H:22]([CH2:26][CH2:27][CH2:28][O:29][CH3:30])[CH2:21]3)=[N:7][C:6]=2[CH:31]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 135525379HCID 135525379, compound

Product 1

HCID 135539058HCID 135539058, compoundYield 77.3%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Combine (S)-8-fluoro-2-trifluoromethyl-11-[3-(3-methoxy-propyl)-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine (0.144 g, 0.330 mmol), formaldehyde (37 μL, 0.461 mmol, 37%), and sodium triacetoxyborohydride (0.105 g, 0.495 mmol) in dichloroethane (5 mL) and stir at room temperature overnight. Dilute the mixture with saturated sodium bicarbonate and extract three times with methylene chloride. Combine the organic layers, dry over sodium sulfate and concentrate under reduced pressure to give the crude product. Purification by flash chromatography, eluting with a step gradient starting with dichloromethane going to 5% 2N ammonia-methanol in dichloromethane gives (S)-8-fluoro-2-trifluoromethyl-11-[3-(3-methoxy-propyl)-4-methyl-piperazin 1-yl]-5H-dibenzo[b,e][1,4]diazepine (0.115 g, 0.255 mmol, 77%) as a yellow oil. Mass spectrum (APCI): m/z=451.3 (M+1). Isolate clean product as the corresponding dihydrochloride in the following manner: dissolve the yellow foam in ethanol (5 mL) and add a solution of about 5 equivalents of HCl in ethanol (5 mL). Evaporate the mixture to obtain (S)-8-fluoro-2-trifluoromethyl-11-[3-(3-methoxy-propyl)-4-methyl-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine dihydrochloride.

Workup

  1. extractionextract three times with methylene chloride
  2. dry with materialdry over sodium sulfate
  3. concentrationconcentrate under reduced pressure
  4. customto give the crude product
  5. customPurification by flash chromatography
  6. washeluting with a step gradient

Sources & evidence

ORD record
ord-cf0e973adfb14d9399d2bc1a8cf89152
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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