Methanol → [(R)-6-fluoro-8-(2-methoxyphenyl)-3,4-dihydro-2H-chromen-2-yl]methanamine

HRID 902318Notes

Reaction equation

HRID 902318 reaction equation
[N:1]([CH2:4][C@H:5]1[CH2:14][CH2:13][C:12]2[C:7](=[C:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[O:22][CH3:23])[CH:9]=[C:10]([F:15])[CH:11]=2)[O:6]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CO>O1CCCC1.O.C(C(Cl)Cl)C.[NH4+].[OH-]>[F:15][C:10]1[CH:11]=[C:12]2[C:7](=[C:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[O:22][CH3:23])[CH:9]=1)[O:6][C@@H:5]([CH2:4][NH2:1])[CH2:14][CH2:13]2

Participants

8

Reactant 3

HCID 887MethanolHCID 11776TriphenylphosphineHCID 86609113(R)-2-azidomethyl-8-(2-methoxyphenyl)-6-fluoro-chroman

Product 1

HCID 15942471[(R)-6-fluoro-8-(2-methoxyphenyl)-3,4-dihydro-2H-chromen-2-yl]methanamine

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 65731,1-DichloropropaneSolventHCID 8028TetrahydrofuranSolventHCID 14923Ammonium HydroxideSolvent

Procedure

To a solution of (R)-2-(azidomethyl)-6-fluoro-8-(2-methoxyphenyl)-chroman (210 mg, 0.67 mmol) in tetrahydrofuran (15 mL) and water (0.5 mL) was added triphenylphosphine (0.21 g, 0.80 mmol) and the reaction mixture stirred at room temperature for 24 hours. Chromatography with 0–10% methanol in ethyl methylene chloride plus 1% NH4OH afforded [(R)-6-fluoro-8-(2-methoxyphenyl)-3,4-dihydro-2H-chromen-2-yl]methanamine as a colorless oil. The oil was dissolved in ethyl acetate and made into its hydrochloride salt (0.95 g, 69%) as a white solid using excess ethereal hydrochloric acid, mp 100° C. decomposed; MS (ES) m/z 288.1 ([M+H]+); [α]D25=−34.64° (c=5.7 mg/0.7 mL MeOH).

Sources & evidence

ORD record
ord-8e5b20030d6648e7a7c80d65b2bf6a29
Source dataset
uspto-grants-2008_04
Patent number
US07365095B2

Reaction notes

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