2-[4-(2-Fluoro-5-iodo-4-methoxyphenyl)piperidin-1-yl]-2-oxoethyl acetate → HCID 86630549, compound

HRID 2093220Notes

Reaction equation

HRID 2093220 reaction equation
[C:1]([O:4][CH2:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[C:18](I)[C:17]([O:21][CH3:22])=[CH:16][C:15]=2[F:23])[CH2:10][CH2:9]1)=[O:7])(=[O:3])[CH3:2].[F:24][C:25]([F:64])([F:63])[C:26]1[CH:27]=[C:28]([C@H:36]2[O:40][C:39](=[O:41])[N:38]([CH2:42][C:43]3[CH:48]=[C:47]([C:49]([F:52])([F:51])[F:50])[CH:46]=[CH:45][C:44]=3B3OC(C)(C)C(C)(C)O3)[C@H:37]2[CH3:62])[CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1.C>[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[C:1]([O:4][CH2:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[C:18]([C:44]3[CH:45]=[CH:46][C:47]([C:49]([F:52])([F:51])[F:50])=[CH:48][C:43]=3[CH2:42][N:38]3[C@@H:37]([CH3:62])[C@@H:36]([C:28]4[CH:29]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:31]=[C:26]([C:25]([F:24])([F:63])[F:64])[CH:27]=4)[O:40][C:39]3=[O:41])[C:17]([O:21][CH3:22])=[CH:16][C:15]=2[F:23])[CH2:10][CH2:9]1)=[O:7])(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 670659912-[4-(2-Fluoro-5-iodo-4-methoxyphenyl)piperidin-1-yl]-2-oxoethyl acetateHCID 86630539HCID 86630539, compound2×

Product 1

HCID 86630549HCID 86630549, compound

Reagents, catalysts & solvents 1

HCID 178454861HCID 178454861, compoundCatalyst

Procedure

A mixture of 2-[4-(2-fluoro-5-iodo-4-methoxyphenyl)piperidin-1-yl]-2-oxoethyl acetate (Step A; 33 mg; 0.076 mmol) and (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one (Intermediate 9; 68 mg, 0.114 mmol) was treated with 1,1′-bis(di-t-butylphosphino)ferrocene palladium dichloride (˜5 mg) as described earlier. The product was purified by chiral HPLC (ChiralPak IA column, 15% IPA/heptane) to afford 2-{4-[2′-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-fluoro-6-methoxy-4′-(trifluoromethyl)biphenyl-3-yl]piperidin-1-yl}-2-oxoethyl acetate as a colorless glass. LCMS=779.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers) δ 7.86 (s, 1 H), 7.69 (s, 2 H), 7.68-7.60 (m, 2 H), 7.32 (d, J=7.8 Hz, 1 H), 6.96-6.91 (m, 1 H), 6.72 (dd, J=11.9, 2.1 Hz, 1 H), 5.59-5.54 (m, 1 H), 4.90 (d, J=15.6 Hz, 1 H), 4.80-4.65 (m, 3 H), 4.13-4.04 (m, 1 H), 3.88-3.72 (m, 2 H), 3.78 (s, 3H), 3.21-3.04 (m, 2H), 2.72-2.67 (m, 1H), 2.17 (s, 3H), 1.96-1.83 (m, 2 H), 1.70-1.59 (m, 2 H), 0.42-0.39 (m, 3 H)

Workup

  1. customThe product was purified by chiral HPLC (ChiralPak IA column, 15% IPA/heptane)

Sources & evidence

ORD record
ord-70abafb16d0048568091941b7a731d54
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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