(3-(Trifluoromethyl)pyridin-2-yl)methanol hydrochloride → (8S)-1'-{[3-(difluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

HRID 1965703Notes

Reaction equation

HRID 1965703 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3[CH:14]=[CH:15][C:16]4[O:17][CH2:18][CH2:19][O:20][C:21]=4[C:12]=3[O:11][CH2:10]2)[C:2]1=[O:22].Cl.CO.Cl.[F:27][C:28](F)([F:37])[C:29]1[C:30]([CH2:35]O)=[N:31][CH:32]=[CH:33][CH:34]=1>>[F:27][CH:28]([F:37])[C:29]1[C:30]([CH2:35][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C@@:3]3([C:13]4[C:12](=[CH:21][C:16]5[O:17][CH2:18][CH2:19][O:20][C:15]=5[CH:14]=4)[O:11][CH2:10]3)[C:2]2=[O:22])=[N:31][CH:32]=[CH:33][CH:34]=1

Participants

4

Reactant 3

HCID 17749867(3-(Trifluoromethyl)pyridin-2-yl)methanol hydrochlorideHCID 21893726Hydrochloride methanolHCID 593523822,3-dihydrospiro[furo[2,3-f][1,4]benzodioxine-7,3'-indol]-2'(1'H)-one

Product 1

HCID 59352666(8S)-1'-{[3-(difluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

Procedure

Following the procedure as described in EXAMPLE 11.78 and making non-critical variations using (8S)-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3-indol]-2′(1′H)-one to replace 2,3-dihydrospiro[furo[2,3-f][1,4]benzodioxine-7,3′-indol]-2′(1′H)-one, and 3-(difluoromethyl)pyridin-2-yl]methanol hydrochloride to replace (3-(trifluoromethyl)pyridin-2-yl)methanol hydrochloride, (8S)-1′-{[3-(difluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one was obtained (50%) as a colorless solid: mp 181-182° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.56 (d, J=4.9 Hz, 1H), 8.08 (d, J=7.7 Hz, 1H), 7.52-7.50 (m, 1H), 7.52-7.42 (m, 1H), 7.25-7.15 (m, 2H), 7.01 (dd, J=7.5, 7.5 Hz, 1H), 6.91 (d, J=7.8 Hz, 1H), 6.51 (s, 1H), 6.42 (s, 1H), 5.18 (ABq, 2H), 4.72 (ABq, 2H), 4.19-4.12 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 177.4, 155.0, 152.9 (t, JC-F=4.3 Hz), 151.4, 144.6, 143.2, 138.2, 135.0 (t, JC-F=7.0 Hz), 132.5, 129.1, 128.0 (t, JC-F=22.6 Hz), 123.9, 123.5, 123.3, 122.0, 113.8 (t, JC-F=236.6 Hz), 112.3, 109.7, 99.1, 79.7, 64.7, 64.1, 57.8, 42.3; MS (ES+) m/z 436.9 (M+1).

Sources & evidence

ORD record
ord-9285170fd9af4d549411788db0835a8c
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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