Formaldehyde → HCID 11742756, compound

HRID 131426Notes

Reaction equation

HRID 131426 reaction equation
C=O.[F:3][C:4]([F:31])([F:30])[C:5]1[CH:29]=[CH:28][C:8]2[NH:9][C:10]3[CH:27]=[CH:26][CH:25]=[CH:24][C:11]=3[N:12]=[C:13]([N:14]3[CH2:19][CH2:18][NH:17][C@@H:16]([CH2:20][CH2:21][O:22][CH3:23])[CH2:15]3)[C:7]=2[CH:6]=1.[C:32](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[F:31][C:4]([F:30])([F:3])[C:5]1[CH:29]=[CH:28][C:8]2[NH:9][C:10]3[CH:27]=[CH:26][CH:25]=[CH:24][C:11]=3[N:12]=[C:13]([N:14]3[CH2:19][CH2:18][N:17]([CH3:32])[C@@H:16]([CH2:20][CH2:21][O:22][CH3:23])[CH2:15]3)[C:7]=2[CH:6]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 10250638(S)-2-Trifluoromethyl-11-[3-(2-methoxy-ethyl)-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine

Product 1

HCID 11742756HCID 11742756, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Add aqueous 37% formaldehyde (1.1 equiv.) to a solution of (S)-2-trifluoromethyl-11-[3-(2-methoxy-ethyl)-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine (470 mg) in dichloroethane (0.2M). Stir the mixture 2 minutes and add sodium triacetoxyborohydride (1.5 equiv). Stir the suspension for 30 minutes and quench with a saturated aqueous solution of sodium bicarbonate. Extract the aqueous phase 3 times with dichloromethane and combine the organic phases, dry over magnesium sulfate, filter and concentrate. Purify the residue via chromatography on silica gel (methylene chloride/methanol (90:10) to afford the title compound as a yellow solid (394 mg, 81%): mp 48-56° C.; 1H NMR (CDCl3): δ 1.70-1.56 (m, 1H), 2.04-1.92 (m, 1H), 2.31 (m, 1H), 2.37 (s, 3H), 2.43 (dt, 1H), 2.81 (t, 1H), 2.89 (d, 1H), 3.13 (t, 1H), 3.25 (s, 3H), 3.38 (t, 2H), 3.73 (bs, 2H), 5.10 (s, 1H), 6.69 (dd, 1H), 6.93-6.88 (m, 2H), 7.00 (dt, 1H), 7.10 (dd, 1H), 7.56-7.50 (m, 2H); MS (ESI/neg) m/z (rel intensity) 417.4 (100).

Workup

  1. stirringStir the suspension for 30 minutes
  2. customquench with a saturated aqueous solution of sodium bicarbonate
  3. extractionExtract the aqueous phase 3 times with dichloromethane
  4. dry with materialdry over magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the residue via chromatography on silica gel (methylene chloride/methanol (90:10)

Sources & evidence

ORD record
ord-ac8e7ba14d5e4837be9aa8dc0a33e9cf
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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