Ammonia → Benzyl 3-[3-(1-aminoethyl)-5-chloro-2-methoxy-6-methylphenyl]azetidine-1-carboxylate

HRID 510935Notes

Reaction equation

[C:1]([C:4]1[C:5]([O:26][CH3:27])=[C:6]([CH:12]2[CH2:15][N:14]([C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])[CH2:13]2)[C:7]([CH3:11])=[C:8]([Cl:10])[CH:9]=1)(=O)[CH3:2].C(O)C.[BH4-].[Na+].[NH3:33]>C([O-])C.C([O-])C.C([O-])C.C([O-])C.[Ti+4]>[NH2:33][CH:1]([C:4]1[C:5]([O:26][CH3:27])=[C:6]([CH:12]2[CH2:15][N:14]([C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])[CH2:13]2)[C:7]([CH3:11])=[C:8]([Cl:10])[CH:9]=1)[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

Titanium tetraethanolate (2.70 mL, 12.9 mmol) was added to a mixture of benzyl 3-(3-acetyl-5-chloro-2-methoxy-6-methylphenyl)azetidine-1-carboxylate (2.5 g, 6.4 mmol) in 2.0 M ammonia in ethanol (16.1 mL, 32.2 mmol) at 0° C. The solution was stirred at 60° C. under N2 overnight. Sodium tetrahydroborate (0.366 g, 9.67 mmol) was added to the above mixture at 0° C. and the solution was stirred at room temperature for another 1 hour. The reaction mixture was quenched with 2 M ammonia in water and filtered. The solid was washed with acetonitrile. The solvent was removed and the residue was diluted with dichloromethane, washed with water and brine, dried over MgSO4 and concentrated to give the desired product (2.47 g, 98%). LCMS calculated for C21H26ClN2O3 (M+H)+: m/z=389.2. found: 389.1.

Workup

stirringthe solution was stirred at room temperature for another 1 hour
customThe reaction mixture was quenched with 2 M ammonia in water
filtrationfiltered
washThe solid was washed with acetonitrile
customThe solvent was removed
additionthe residue was diluted with dichloromethane
washwashed with water and brine
dry with materialdried over MgSO4
concentrationconcentrated

Sources & evidence

ORD record: ord-98bfd4a1fc2d4a989e00e4ec038878ad
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096600B2

Reaction notes

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