2-(Bromomethyl)tetrahydro-2H-pyran → 5-fluoro-6-methoxy-1'-[(2R)-tetrahydrofuran-2-ylmethyl]spiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

HRID 1965524Notes

Reaction equation

HRID 1965524 reaction equation
[F:1][C:2]1[C:3]([O:20][CH3:21])=[CH:4][C:5]2[O:19][CH2:18][C:8]3([C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[NH:10][C:9]3=[O:17])[C:6]=2[CH:7]=1.CC1C=CC(S(O[CH2:33][C@H:34]2[CH2:38][CH2:37][CH2:36][O:35]2)(=O)=O)=CC=1.BrCC1CCCCO1>>[F:1][C:2]1[C:3]([O:20][CH3:21])=[CH:4][C:5]2[O:19][CH2:18][C:8]3([C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]([CH2:33][C@H:34]4[CH2:38][CH2:37][CH2:36][O:35]4)[C:9]3=[O:17])[C:6]=2[CH:7]=1

Participants

4

Reactant 3

HCID 1419172-(Bromomethyl)tetrahydro-2H-pyranHCID 7033050(R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonateHCID 461940485-fluoro-6-methoxyspiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

Product 1

HCID 593521745-fluoro-6-methoxy-1'-[(2R)-tetrahydrofuran-2-ylmethyl]spiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

Procedure

Following the procedure as described in EXAMPLE 4 and making non-critical variations using 5-fluoro-6-methoxyspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one to replace 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2″(1′H)-one, and (R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate to replace 2-(bromomethyl)tetrahydro-2H-pyran, 5-fluoro-6-methoxy-1′-[(2R)-tetrahydrofuran-2-ylmethyl]spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one was obtained (42%) as a colorless solid: mp 106-116° C.; 1H NMR (300 MHz, CDCl3) δ7.28 (dd, J=7.6, 7.6 Hz, 1H), 7.14-6.98 (m, 3H), 6.58 (d, J=6.8 Hz, 1H), 6.49-6.40 (m, 1H), 4.92 (d, J=9.0 Hz, 1H), 4.66 (d, J=9.0 Hz, 1H), 4.31-4.19 (m, 1H), 3.98-3.64 (m, 7H), 2.09-1.80 (m, 3H), 1.76-1.61 (m, 1H); 13C NMR (75 MHz, CDCl3) δ177.7, 177.5, 157.1, 149.3, 149.1, 148.9, 146.1, 142.8, 131.9, 131.7, 129.0, 128.9, 123.7, 123.6, 123.3, 119.3, 119.2, 110.6, 110.5, 110.3, 110.2, 109.8, 109.6, 96.3, 80.6, 76.7, 68.2, 68.1, 58.0, 56.4, 44.6, 29.2, 29.0, 25.7, 25.5; MS (ES+) m/z 370.2 (M+1).

Sources & evidence

ORD record
ord-973066f26ebe4ffb9b9f2afe3905c867
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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