2-(Bromomethyl)-5-(trifluoromethyl)furan → 6'-fluoro-1'-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1H)-one

HRID 2385371Notes

Reaction equation

HRID 2385371 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([CH2:15][O:14][C:13]4[CH:16]=[C:17]5[C:21](=[CH:22][C:12]3=4)[CH2:20][CH2:19][O:18]5)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.CC1C2C=[C:30]3[C:35]4(C5C(=CC=CC=5)NC4=O)[CH2:34][O:33][C:31]3=[CH:32]C=2ON=1.CC1C=CC(S(OC[C@H]2CCCO2)(=O)=O)=CC=1.BrCC1OC(C(F)(F)F)=CC=1>>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([CH2:15][O:14][C:13]4[CH:16]=[C:17]5[C:21](=[CH:22][C:12]3=4)[CH2:20][CH2:19][O:18]5)[C:7](=[O:11])[N:8]2[CH2:32][C@H:31]2[CH2:30][CH2:35][CH2:34][O:33]2)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 27946052-(Bromomethyl)-5-(trifluoromethyl)furanHCID 7033050(R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonateHCID 593522606'-fluoro-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1'H)-oneHCID 593524533-methylspiro[furo[3,2-f][1,2]benzisoxazole-5,3'-indol]-2'(1H)-one

Product 1

HCID 685990116'-fluoro-1'-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-indol]-2'(1H)-one

Procedure

Following the procedure as described in EXAMPLE 9 and making non-critical variations using 6′-fluoro-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one to replace 3-methylspiro[furo[3,2-f][1,2]benzisoxazole-5,3′-indol]-2′(1′H)-one, and (R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate to replace 2-(bromomethyl)-5-(trifluoromethyl)furan, 6′-fluoro-1′-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one was obtained (47%) as a colorless solid: mp 137-139° C. (diethyl ether/hexanes); 1H NMR (300 MHz, CDCl3) 7.08-7.03 (m, 1H), 6.88-6.83 (m, 1H), 6.73-6.66 (m, 1H), 6.46 (s, 1H), 6.38 (s, 1H), 4.74 (ABq, 2H), 4.52 (t, J=9.0 Hz, 2H), 4.25-4.20 (m, 1H), 3.96-3.60 (m, 4H), 2.98 (t, J=9.0 Hz, 2H), 2.08-1.86 (m, 3H), 1.73-1.64 (m, 1H); 13C NMR (75 MHz, CDCl3) δ178.0, 161.9, 161.2, 128.1, 124.7, 120.0, 118.8, 109.5, 109.2, 98.8, 98.4, 93.2, 80.6, 72.4, 68.3, 57.3, 44.8, 29.2, 28.9, 25.7; MS (ES+) m/z 382.0 (M+1).

Sources & evidence

ORD record
ord-56711b35e44e49c0b7717062625779dc
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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