Methylamine → (S)-ethyl 2-tert-butoxy-2-(7-fluoro-3-methyl-6-(methylcarbamoyl)-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate

HRID 514107ノート

反応式

HRID 514107 の反応式
[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][C:16]([F:24])=[C:17](Cl)[CH:18]=2)[C:13]=1[O:25][S:26]([C:29]([F:32])([F:31])[F:30])(=[O:28])=[O:27])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].CN.C1[CH2:39][O:38]CC1.[CH2:40]([N:42](CC)CC)C>C(OCC)(=O)C.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].C1(C)C=CC=CC=1>[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][C:16]([F:24])=[C:17]([C:39](=[O:38])[NH:42][CH3:40])[CH:18]=2)[C:13]=1[O:25][S:26]([C:29]([F:32])([F:31])[F:30])(=[O:28])=[O:27])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

参加物

9

反応物 4

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 86691553(S)-ethyl 2-tert-butoxy-2-(6-chloro-7-fluoro-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate

生成物 1

HCID 86691558(S)-ethyl 2-tert-butoxy-2-(7-fluoro-3-methyl-6-(methylcarbamoyl)-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate収率 13.9%

試薬・触媒・溶媒 4

HCID 98885Molybdenum carbonyl (Mo(CO)6)触媒HCID 25112666BrettPhos Palladacycle触媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
140 °C

実験手順

A Smith process vial was charged with (S)-ethyl 2-tert-butoxy-2-(6-chloro-7-fluoro-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate (131.8 mg, 0.263 mmol), 2 M methylamine in THF (0.66 mL, 1.32 mmol), molybdenum hexacarbonyl (0.069 g, 0.263 mmol), BrettPhos Palladacycle (29 mg, 0.0395 mmol), and triethylamine (0.128 mL, 0.921 mmol). Toluene (1.5 mL) was added and mixture was heated in microwave at 140° C. for 1.5 hour. The reaction mixture was diluted with ethyl acetate, washed brine, dried (MgSO4), filtered, concentrated and purified by flash column chromatography (silica gel, 0 to 50% ethyl acetate/hexanes) to give an off-white solid (19.2 mg). LCMS-ESI+ (m/z): [M+H]+ calcd for C22H26F4NO7S: 524.5; Found: 524.0.

後処理

  1. washwashed brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (silica gel, 0 to 50% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-6441d4f8f2a74b48a4ab09291605ee4a
出典データセット
uspto-grants-2015_08
特許番号
US09102614B2

反応ノート

読み込み中…