Potassium Carbonate → (4S,5R)-3-({6-azetidin-1-yl-3-[5-(hydroxymethyl)-2-methoxyphenyl]pyridin-2-yl}methyl)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1508581ノート

反応式

HRID 1508581 の反応式
[N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])[C:8](Br)=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[CH3:34][O:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42][OH:43])=[CH:38][C:37]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.[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]>[N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])[C:8]([C:37]3[CH:38]=[C:39]([CH2:42][OH:43])[CH:40]=[CH:41][C:36]=3[O:35][CH3:34])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 60126753(4-Methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanol2 回HCID 86704598(4S,5R)-3-[(6-azetidin-1-yl-3-bromopyridin-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one2 回

生成物 1

HCID 86704629(4S,5R)-3-({6-azetidin-1-yl-3-[5-(hydroxymethyl)-2-methoxyphenyl]pyridin-2-yl}methyl)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

試薬・触媒・溶媒 2

HCID 178454861HCID 178454861、化合物触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

A mixture of (4S,5R)-3-[(6-Azetidin-1-yl-3-bromopyridin-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 35) (943 mg, 1.752 mmol), [4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanol (EXAMPLE 258, Step A) (555 mg, 2.102 mmol), potassium carbonate (1M aqueous) (4 ml, 4.00 mmol), and 1,1′-bis(di-t-butylphosphino)ferrocene palladium dichloride (114 mg, 0.175 mmol) in THF (12 ml) was stirred at 60° C. with microwaves for 1 hour. 125 mg of [4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanol were added and the heating continued for another 30 minutes. The reaction mixture was filtered through a silica plug washing with EtOAc and concentrated. The residue was purified by flash column chromatography on silica gel, eluting with EtOAc in hexanes. A second purification using RP HPLC afforded the pure title compound. Mass spectrum (ESI) 596.3 (M+1). 1H NMR (500 MHz, CD3OD): δ 7.96 (s, 1H); 7.88 (s, 2H); 7.32 (d, J=8.2 Hz, 2H); 7.16 (s, 1H); 7.01 (d, J=8.2 Hz, 1H); 6.35 (d, J=8.3 Hz, 1H); 5.72 (m, 1H); 4.65 (d, J=16.3 Hz, 1H); 4.55 (s, 2H); 4.23 (s, 1H); 4.05 (t, J=7.3 Hz, 4H); 3.90 (br s, 1H); 3.77 (s, 2H); 2.43-2.36 (m, 2H); 0.60 (s, 3H).

後処理

  1. waitthe heating continued for another 30 minutes
  2. filtrationThe reaction mixture was filtered through a silica plug
  3. washwashing with EtOAc
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography on silica gel
  6. washeluting with EtOAc in hexanes
  7. customA second purification

出典と根拠

ORDレコード
ord-ca6078db5d9941ff997ef4f520a4ac18
出典データセット
uspto-grants-2015_12
特許番号
US09221834B2

反応ノート

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