2-(Bromomethyl)tetrahydro-2H-pyran → tert-butyl 4-[(5,6-difluoro-2'-oxospiro[1-benzofuran-3,3-indol]-1'(2'H)-yl)methyl]piperidine-1-carboxylate

HRID 2385295Notes

Reaction equation

HRID 2385295 reaction equation
S(O[CH2:12][CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1)(C1C=CC(C)=CC=1)(=O)=O.BrCC1CCCCO1.[F:34][C:35]1[C:36]([F:53])=[CH:37][C:38]2[O:52][CH2:51][C:41]3([C:49]4[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=4)[NH:43][C:42]3=[O:50])[C:39]=2[CH:40]=1.N1C2C(=CC=CC=2)C2(COC3C=C4C(=CC2=3)CCO4)C1=O>>[F:34][C:35]1[C:36]([F:53])=[CH:37][C:38]2[O:52][CH2:51][C:41]3([C:49]4[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=4)[N:43]([CH2:12][CH:13]4[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])[CH2:17][CH2:18]4)[C:42]3=[O:50])[C:39]=2[CH:40]=1

Participants

5

Reactant 4

HCID 1419172-(Bromomethyl)tetrahydro-2H-pyranHCID 106428511-(tert-Butoxycarbonyl)-4-((p-toluenesulfonyloxy)methyl)piperidineHCID 592633545,6-dihydro-2H-spiro[benzofuro[6,5-b]furan-3,3'-indolin]-2'-oneHCID 593525695,6-difluorospiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

Product 1

HCID 59352356tert-butyl 4-[(5,6-difluoro-2'-oxospiro[1-benzofuran-3,3-indol]-1'(2'H)-yl)methyl]piperidine-1-carboxylate

Procedure

Following the procedure as described in EXAMPLE 4 and making non-critical variations using tert-butyl 4-(tosyloxymethyl)piperidine-1-carboxylate to replace 2-(bromomethyl)tetrahydro-2H-pyran, and 5,6-difluorospiro[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, tert-butyl 4-[(5,6-difluoro-2′-oxospiro[1-benzofuran-3,3′-indol]-1′(2′H)-yl)methyl]piperidine-1-carboxylate was obtained (57%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 7.34 (ddd, J=9.0, 7.6, 1.5 Hz, 1H), 7.16-7.06 (m, 2H), 6.92 (d, J=7.8 Hz, 1H), 6.78 (dd, J=10.3, 6.3 Hz, 1H), 6.49 (dd, J=10.3, 6.3 Hz, 1H), 4.95 (d, J=9.0 Hz, 1H), 4.70 (d, J=9.0 Hz, 1H), 4.13 (br s, 2H), 3.74-3.56 (m, 2H), 2.69 (t, J=12.4 Hz, 2H), 2.07-1.96 (m, 1H), 1.68-1.63 (m, 2H), 1.45 (s, 9H), 1.32-1.26 (m, 2H); MS (ES+) m/z 493.3 (M+23).

Sources & evidence

ORD record
ord-8d73cd457fbb4ea295e4bdd5fbce3792
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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