(S)-2-(iodomethyl)-1,4-dioxane → 1'-[(2R)-1,4-dioxan-2-ylmethyl]-3,4-dihydro-2H-spiro[furo[2,3-h][1,5]benzodioxepine-9,3'-indol]-2'(1'H)-one

HRID 1965617Notes

Reaction equation

HRID 1965617 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][C:15]4[O:21][CH2:20][CH2:19][CH2:18][O:17][C:16]=4[CH:22]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:23].N1C2C(=CC=CC=2)C2(C3=CC4OCOC=4C=C3OC2)C1=O.I[CH2:46][C@@H:47]1[CH2:52][O:51][CH2:50][CH2:49][O:48]1.CC1C=CC(S(OC[C@H]2COCCO2)(=O)=O)=CC=1>>[O:48]1[CH2:49][CH2:50][O:51][CH2:52][C@H:47]1[CH2:46][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:21][CH2:20][CH2:19][CH2:18][O:17][C:16]=4[CH:22]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:23]

Participants

5

Reactant 4

HCID 26338661(S)-2-(iodomethyl)-1,4-dioxaneHCID 461939253,4-dihydro-2H-spiro[furo[2,3-h][1,5]benzodioxepine-9,3'-indol]-2'(1'H)-oneHCID 53375495spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-oneHCID 59253203(R)-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 461939221'-[(2R)-1,4-dioxan-2-ylmethyl]-3,4-dihydro-2H-spiro[furo[2,3-h][1,5]benzodioxepine-9,3'-indol]-2'(1'H)-one

Procedure

Following the procedure as described in EXAMPLE 8 and making non-critical variations using 3,4-dihydro-2H-spiro[furo[2,3-h][1,5]benzodioxepine-9,3′-indol]-2′(1′H)-one to replace spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one, and (S)-2-(iodomethyl)-1,4-dioxane to replace (R)-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate, 1′-[(2R)-1,4-dioxan-2-ylmethyl]-3,4-dihydro-2H-spiro[furo[2,3-h][1,5]benzodioxepine-9,3′-indol]-2′(1′H)-one was obtained (61%) as a colorless solid: mp 144-147° C. (diethyl ether/hexanes); 1H NMR (300 MHz, CDCl3) (diastereomers) δ 7.30 (ddd, J=7.7, 7.7, 1.0 Hz, 1H), 7.14 (d, J=6.9 Hz, 1H), 7.08-7.02 (m, 2H), 6.59 (s, 1H), 6.36, 6.33 (s, 1H), 4.91, 4.90 (d, J=9.0 Hz, 1H), 4.67, 4.66 (d, J=9.0 Hz, 1H), 4.28-4.19 (m, 1H), 4.15-4.02 (m, 2H), 3.99-3.78 (m, 5H), 3.75-3.57 (m, 4H), 3.46-3.39 (m, 1H), 2.22-2.00 (m, 2H); 13C NMR (75 MHz, CDCl3) (diastereomers) δ177.8, 177.7, 156.8, 156.7, 153.1, 153.0, 146.4, 146.3, 142.65, 142.63, 132.3, 132.2, 129.0, 128.9, 124.0, 123.9, 123.6, 123.2, 123.1, 116.1, 116.0, 109.6, 109.4, 103.58, 103.56, 80.5, 80.4, 73.34, 73.30, 70.9, 69.4, 69.2, 66.8, 66.7, 66.52, 66.49, 57.98, 57.96, 41.9, 41.8, 32.3; MS (ES+) m/z 410.0 (M+1).

Sources & evidence

ORD record
ord-f9d5925cf35d42f698609dd87a708e06
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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