Benzenemethanamine, 3-chloro- → (RS)-(3-chloro-benzyl)-[3-(5-methoxy-3-methyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-phenyl]-amine

HRID 593345Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:8]2([CH3:16])[N:13]=[C:12]([O:14][CH3:15])[CH2:11][O:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.[Cl:47][C:48]1[CH:49]=[C:50]([CH:53]=[CH:54][CH:55]=1)[CH2:51][NH2:52]>C1(C)C=CC=CC=1>[Cl:47][C:48]1[CH:49]=[C:50]([CH:53]=[CH:54][CH:55]=1)[CH2:51][NH:52][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2([CH3:16])[N:13]=[C:12]([O:14][CH3:15])[CH2:11][O:10][CH2:9]2)[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A dried pressure tube was charged consecutively under a nitrogen atmosphere with a solution of (RS)-3-(3-bromo-phenyl)-5-methoxy-3-methyl-3,6-dihydro-2H [1,4]oxazine (150 mg, 0.5 mmol) in toluene (5 ml), sodium tert-butylate (157 mg, 1.6 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (tert-butyl-x-phos) (23 mg, 0.1 mmol), tris(dibenzylideneacetone)-dipalladium chloroform complex (17 mg), and 3-chlorobenzylamine (154 mg, 1.1 mmol). The sealed pressure tube was heated at 100° C. for 15 hours. After cooling, the reaction mixture was evaporated to dryness and directly purified by chromatography on an Isolute flash NH2 column using a gradient of heptane/ethyl acetate=100/0 to 50/50 as the eluent. 85 mg (47%) of (RS)-(3-chloro-benzyl)-[3-(5-methoxy-3-methyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-phenyl]-amine were obtained as a yellow oil. Mass (calculated) C19H21ClN2O2 [344.844]; (found) [M+H]+=345.

Workup

temperatureAfter cooling
customthe reaction mixture was evaporated to dryness
customdirectly purified by chromatography on an Isolute flash NH2 column

Sources & evidence

ORD record: ord-6e418ac078b24d3d809f4d33867c2e31
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242943B2

Reaction notes

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