Hydrochloric Acid → (+/-)-1-[7-(2,3-Dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine

HRID 2116210Notes

Reaction equation

HRID 2116210 reaction equation
CC1C=CC(S(O[CH2:12][CH:13]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[C:23]=4[CH3:29])[C:15]=3[O:14]2)(=O)=O)=CC=1.[N-:30]=[N+]=[N-].[Na+].N(CC1CC2C=CCC(C3C=CC=C(Cl)C=3Cl)(N)C=2O1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>O1CCCC1.C(O)(C)C>[CH3:29][C:23]1[C:24]([CH3:28])=[CH:25][CH:26]=[CH:27][C:22]=1[C:21]1[C:15]2[O:14][CH:13]([CH2:12][NH2:30])[CH2:17][C:16]=2[CH:18]=[CH:19][CH:20]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 86599147(+/-)-[7-(2,3-Dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonateHCID 86599249(+/-)-2-(Azidomethyl)-7-(2,3-dichlorophenyl)-2,3-dihydro-1-benzofuran-7 amine2×

Product 1

HCID 11357234(+/-)-1-[7-(2,3-Dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamineYield 54%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Treatment of (±)-(7-bromo-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.305 mmol) with (2,3-dimethyl-phenyl)boronic acid (0.294 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.041 g, 0.052 mmol), and potassium carbonate (0.41 g, 3.25 mmol) generally according to the procedure described for Intermediate 37 provided 0.335 g (62%) of (±)-[7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate. Treatment of (±)-[7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methyl 4-methylbenzenesulfonate with sodium azide (0.134 g, 2.06 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2-(azidomethyl)-7-(2,3-dichlorophenyl)-2,3-dihydro-1-benzofuran-7 amine. To a solution of (±)-2-(azidomethyl)-7-(2,3-dichlorophenyl)-2,3-dihydro-1-benzofuran-7 amine (0.135 g, 1.483 mmol) in tetrahydrofuran (5 mL) was added polymer supported triphenyl phosphine (0.152 g, 0.58 mmol) and the reaction mixture was allowed to stir at room temperature for 12 h. The reaction mixture was filtered (celite) and the solvent removed in vacuo to provide a colorless oil. The oil was re-dissolved in isopropanol (3 mL) and hydrogen chloride (1.0 N in diethyl ether, 10.0 mL) was added. The resulting precipitate was filtered, washed (diethyl ether), and dried to afford 0.075 g (54%) of (±)-1-[7-(2,3-dimethylphenyl)-2,3-dihydro-1-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt. mp >225° C.:

Workup

  1. filtrationThe reaction mixture was filtered (celite)
  2. customthe solvent removed in vacuo
  3. customto provide a colorless oil
  4. filtrationThe resulting precipitate was filtered
  5. washwashed (diethyl ether)
  6. customdried

Sources & evidence

ORD record
ord-815805dda20c443da066224276166613
Source dataset
uspto-grants-2008_10
Patent number
US07435837B2

Reaction notes

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