Sodium Carbonate → 1,1-Dimethylethyl 4-{[(2'-fluoro-6'-methyl-2,3'-bipyridin-5-yl)oxy]methyl}-1-piperidine carboxylate

HRID 423615Notes

Reaction equation

HRID 423615 reaction equation
[F:1][C:2]1[C:7](B(O)O)=[CH:6][CH:5]=[C:4]([CH3:11])[N:3]=1.Br[C:13]1[N:18]=[CH:17][C:16]([O:19][CH2:20][CH:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)=[CH:15][CH:14]=1.C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[C:7]([C:13]2[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH:21]3[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH2:26]3)=[CH:17][N:18]=2)=[CH:6][CH:5]=[C:4]([CH3:11])[N:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27631322-Fluoro-6-methylpyridine-3-boronic acidHCID 579302011,1-Dimethylethyl 4-{[(6-bromo-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate

Product 1

HCID 666732201,1-Dimethylethyl 4-{[(2'-fluoro-6'-methyl-2,3'-bipyridin-5-yl)oxy]methyl}-1-piperidine carboxylate

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Procedure

1,1-Dimethylethyl 4-{[(2′-fluoro-6′-methyl-2,3′-bipyridin-5-yl)oxy]methyl}-1-piperidinecarboxylate (0.21 g, 72%) was prepared as an off-white solid from 2-fluoro-6-picoline-3-boronic acid (0.14 g, 0.87 mmol), 1,1-dimethylethyl 4-{[(6-bromo-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate (prepared as in Example 76, Step 1, 0.27 g, 0.72 mmol), 2M Na2CO3 (2.5 mL) and PdCl2(PPh3)2 (26 mg, 0.04 mmol) DME (8 mL) in a manner similar to Example 21, Step 3. The crude material was purified by chromatography on a silica gel column eluted with 1:10 acetone/CH2Cl2 to give 1,1-dimethylethyl 4-{[(2′-fluoro-6′-methyl-2,3′-bipyridin-5-yl)oxy]methyl}-1-piperidine carboxylate as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 8.45-8.35 (m, 2H), 7.81 (d, 1H, J=8.0 Hz), 7.30-7.25 (m, 1H), 7.15-7.10 (m, 1H), 4.16 (bs, 2H), 3.88 (d, 2H, J=6.4 Hz), 2.80-2.65 (m, 2H), 2.53 (s, 3H), 2.10-1.90 (m, 1H), 1.90-1.80 (m, 2H), 1.45 (s, 9H), 1.35-1.20 (m, 2H); LRMS (ESI), m/z 402 (M+H).

Workup

  1. customThe crude material was purified by chromatography on a silica gel column
  2. washeluted with 1:10 acetone/CH2Cl2

Sources & evidence

ORD record
ord-f2a4161f5e194b98a1ff85ff580909e1
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

Loading…