Water → 4-(((3-Fluoro)benzyloxy)methyl)benzylamine

HRID 1425714Notes

Reaction equation

HRID 1425714 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[F:7][C:8]1[CH:9]=[C:10]([CH:22]=[CH:23][CH:24]=1)[CH2:11][O:12][CH2:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1.O.[OH-].[Na+]>C1COCC1>[F:7][C:8]1[CH:9]=[C:10]([CH:22]=[CH:23][CH:24]=1)[CH2:11][O:12][CH2:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18][NH2:19])=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 462235894-((3-Fluorobenzyloxy)methyl)benzonitrile

Product 1

HCID 462235904-(((3-Fluoro)benzyloxy)methyl)benzylamineYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a LiAlH4 (2.00 g, 53.4 mmol) suspension in THF (300 mL) was added dropwise a THF (20 mL) solution of 4-(((3-fluoro)benzyloxy)methyl)benzonitrile (4.30 g, 17.8 mmol) at 0° C. The mixture was stirred at room temperature (16 h) and H2O (1.6 mL) was added dropwise at 0° C. followed by an aqueous NaOH solution (0.8 mL, 15% w/w), and then H2O (1.6 mL). The mixture was stirred at room temperature (2 h), and the precipitate filtered and washed with CH2Cl2. The filtrate was concentrated in vacuo and the solid triturated with Et2O to obtain a white solid (1.60 g, 37%). The solid was used in the next step with no other purification: Rf=: 0.00 (hexanes/EtOAc 8/2); mp>138° C. (decomp.); IR (nujol) 3224, 3100, 3039, 2970, 2843, 1593, 1520, 1456, 1375, 1257, 1143, 1073, 940, 866, 733, 686, 549 cm−1; 1H NMR (CDCl3) δ 3.87 (s, CH2NH2), 4.47-4.54 (m, 2 CH2O), 7.08-7.45 (m, 8 ArH); 13C NMR (CDCl3) δ 43.1 (CH2N), 70.4, 71.2 (2 CH2O), 113.8 (d, J=21.7 Hz, C2′ or C4′), 114.1 (d, J=20.5 Hz, C4′ or C2′), 123.1 (d, J=2.3 Hz, C6′), 127.5 (ArC), 128.1 (ArC), 130.2 (d, J=8.0 Hz, C5′), 137.2, 137.3 (2 ArC), 141.4 (d, J=6.8 Hz, C1′), 162.1 (d, J=242.5 Hz, C3′); HRMS (M+H+)(ESI+) 246.1294 [M+H+] (calcd for C15H16FNOH+ 246.1294).

Workup

  1. additionwas added dropwise at 0° C.
  2. filtrationthe precipitate filtered
  3. washwashed with CH2Cl2
  4. concentrationThe filtrate was concentrated in vacuo
  5. customthe solid triturated with Et2O

Sources & evidence

ORD record
ord-368d302ec703444eae153b5198e7d9aa
Source dataset
uspto-grants-2015_01
Patent number
US08933065B2

Reaction notes

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