Tributyltin Chloride → HCID 51002308, compound

HRID 2167916Notes

Reaction equation

HRID 2167916 reaction equation
Cl.[Cl:2][C:3]1[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[C:4]=1[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[O:18][CH2:17][CH2:16][N:15]([CH2:19][CH2:20][C:21]3[N:22]=[N:23][NH:24][N:25]=3)[CH2:14]2)=[CH:9][CH:8]=1.ClC1C=CC=C(Cl)C=1COC1C=CC(C2OCCN(CCC#N)C2)=CC=1.C([Sn](Cl)(CCCC)CCCC)CCC.[N-]=[N+]=[N-].[Na+]>C1(C)C(C)=CC=CC=1.CO>[Cl:2][C:3]1[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[C:4]=1[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([CH:13]2[O:18][CH2:17][CH2:16][N:15]([CH2:19][CH2:20][C:21]3[N:22]=[N:23][NH:24][N:25]=3)[CH2:14]2)=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 15096Tributyltin ChlorideHCID 33557Sodium AzideHCID 67032227HCID 67032227, compoundHCID 67032272HCID 67032272, compound

Product 1

HCID 51002308HCID 51002308, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 7237O-XyleneSolvent

Conditions

Temperature
120 °C

Procedure

2-[4-(2,6-Dichloro-benzyloxy)-phenyl]-4-[2-(2H-tetrazol-5-yl)-ethyl]-morpholine hydrochloride: To a solution of 3-{2-[4-(2,6-dichloro-benzyloxy)-phenyl]-morpholin-4-yl}-propionitrile (0.30 g; 0.77 mmol) in xylene (10 mL) was added tributyltin chloride (0.46 mL; 1.7 mmol) and NaN3 (110 mg; 1.7 mmol). The resulting mixture was heated at 120° C. for two days. After cooling to RT the mixture was treated with methanol (10 mL) and concentrated in vacuo. The residue was purified by column chromatography (EtOAc:methanol 90:10 to 50:50) to afford 2-[4-(2,6-dichloro-benzyloxy)-phenyl]-4-[2-(2H-tetrazol-5-yl)-ethyl]-morpholine as the free base (0.30 g), The free base was treated with a solution of HCl in 1,4-dioxane, after stirring at RT for 4 hours, the salt precipitated. The salt was collected by filtration, washed with Et2O and dried in vacuo to afford 2-[4-(2,6-dichloro-benzyloxy)-phenyl]-4-[2-(2H-tetrazol-5-yl)-ethyl]-morpholine hydrochloride (0.30 g). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.15-3.29 (m, 2H) 3.53-3.75 (m, 6H) 4.06-4.22 (m, 2H) 4.94 (d, J=11.0 Hz, 1H) 5.24 (s, 2H) 7.11 (d, J=8.6 Hz, 2H) 7.36 (d, J=8.6 Hz, 2H) 7.45-7.52 (m, 1H) 7.58 (d, J=8.3 Hz, 2H) 12.31 (bs, 1H).

Workup

  1. temperatureAfter cooling to RT the mixture
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by column chromatography (EtOAc:methanol 90:10 to 50:50)

Sources & evidence

ORD record
ord-66098e034e8f4f7fb8ec153d6b9b361a
Source dataset
uspto-grants-2015_06
Patent number
US09045441B2

Reaction notes

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