Formaldehyde → HCID 21071654, compound

HRID 1666861Notes

Reaction equation

HRID 1666861 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:11][CH2:12][NH:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][CH:23]([F:25])[F:24])[CH:16]=3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C=O.[C:28](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:11][CH2:12][N:13]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][CH:23]([F:25])[F:24])[CH:16]=3)[CH3:28])=[CH:7][NH:8]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 21071426HCID 21071426, compound

Product 1

HCID 21071654HCID 21071654, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 63651,1-DichloroethaneSolvent

Procedure

Combine N-(2-(6-chloro-1H-indol-3-yl)ethyl)-3-(2,2-difluoroethoxy)benzylamine (276 mg, 0.76 mmol) and formaldehyde (55.5 μL of a 38% aqueous solution, 0.76 mmol) in dichloroethane (15 mL) and stir at room temperature for 10 minutes; then add in two portions over 10 minutes sodium triacetoxyborohydride (321 mg, 1.51 mmol). Stir the reaction mixture at room temperature overnight and dilute with methanol (10 mL) and quench with one drop of glacial acetic acid. Remove the solvent in vacuo, to give a residue, redissolve the crude residue in methanol and directly load onto a 10 g SCX column. After washing the column thoroughly with methanol, elute with 2 N ammonia in methanol. Concentrate in vacuo to give the title compound as an oil. Dissolve the oil (239 mg, 0.64 mmol) in methanol (20 mL) and treat with a solution of ammonium chloride (36 mg, 0.67 mmol) in methanol (5 mL). Sonicate the mixture for 10 minutes before removal of the solvent in vacuo to give the title compound as the hydrochloride salt Dissolve the salt in 10 mL of 1:1 acetonitrile-water and lyophilize overnight, providing a fluffy white solid. Triturate the solid with diethyl ether (10 mL) and acetonitrile (2 drops), filter, and dry to give the title compound as the hydrochloride salt: mp: 63.8-65.8° C.; 1H NMR (400 MHz, dmso-d6): 11.10 (br s, 1H), 7.52 (d, 1H, J=8.4 Hz) 7.36 (d, 1H, J=2.0 Hz), 7.40-7.26 (m, 2H), 7.22 (d, 1H, J=2.4 Hz), 7.20-7.11 (m, 1H), 7.04 (br d, 1H, J=7.6 Hz), 6.96 (dd, 1H, J=8.6, 1.4 Hz), 6.38 (tt, 1H, J=54.4, 3.6, Hz), 4.50-4.02 (br m, 2H), 4.30 (td, 2H, J=14.4, 3.2 Hz), 3.15 (br s, 4H), 2.68 (br s, 3H); MS (ES+): m/e 378.9 (M+1.

Workup

  1. customquench with one drop of glacial acetic acid
  2. customRemove the solvent in vacuo
  3. customto give a residue
  4. washAfter washing the column thoroughly with methanol
  5. washelute with 2 N ammonia in methanol
  6. concentrationConcentrate in vacuo

Sources & evidence

ORD record
ord-b046048b4dfa48a9b9931f0497bd842b
Source dataset
uspto-grants-2011_10
Patent number
US08044090B2

Reaction notes

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