Tetrahydrofuran → tert-Butyl 6-[(6-methylpyridin-2-yl)methyl]-1,4-oxazepane-4-carboxylate

HRID 401817

反応式

HRID 401817 の反応式
CCCCCCCCC.C1COCC1.C1(CO[CH2:20][C:21]2(O)[CH2:27][O:26][CH2:25][CH2:24][N:23]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:22]2)CC1.Br[C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[N:38]=1.C(=O)([O-])[O-].[K+].[K+]>CCCCCC.C(Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:43][C:39]1[N:38]=[C:37]([CH2:20][CH:21]2[CH2:27][O:26][CH2:25][CH2:24][N:23]([C:28]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:29])[CH2:22]2)[CH:42]=[CH:41][CH:40]=1

参加物

9

反応物 5

HCID 8028TetrahydrofuranHCID 8141NonaneHCID 11430Potassium CarbonateHCID 792052-Bromo-6-methylpyridineHCID 68531565Tert-butyl 6-[(cyclopropylmethoxy)methyl]-6-hydroxy-1,4-oxazepane-4-carboxylate

生成物 1

HCID 86630785tert-Butyl 6-[(6-methylpyridin-2-yl)methyl]-1,4-oxazepane-4-carboxylate

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 6344Dichloromethane溶媒HCID 8058Hexane溶媒

実験手順

0.5M 9-Borobicyclo[3.3.1]nonane in THF (415 mL, 0.21 mol, 1.1 eq) was added under stirring in a stream of argon at room temperature to tert-butyl 6-[(cyclopropylmethoxy)methyl]-6-hydroxy-1,4-oxazepane-4-carboxylate (Preparation 80, 40 g, 0.19 mol, 1 eq). The reaction mixture was stirred at room temperature for 2 h. After this, the catalyst palladium (0) tetrakis(triphenylphosphine) (4 g, 0.003 mol, 0.02 eq) and 2-bromo-6-methylpyridine (36 g, 0.21 mmol, 1.1 eq) were added to the mixture, and the latter was stirred for 15 min. Then 3M potassium carbonate solution (125 mL, 0.38 mol, 2 eq) was added, and the reaction mixture was refluxed for 3 h. The mixture was cooled, diluted with hexane (300 mL) and DCM (100 mL). The organic layer was separated, washed with water (2×100 mL), and with the saturated sodium chloride solution. The combined aqueous layer was extracted with ethyl acetate/hexane (3:1) mixture (2×200 mL). The organic layers were sequentially filtered through silica (25 g; 63-100 μm) and sodium sulphate (50 g) and evaporated. The residue was subjected to chromatography (carbon tetrachloride/chloroform/isopropanol 100:0:0→90:10:0→70:30:0→50:50:0→30:70:0→0:100:0→0:99:1→0:98:2→0:97:3→0:95:5→0:93:7→0:92:8→0:90:10) on silica (500 g; 63-100 μm). The fractions, containing the product, were collected and evaporated to give title compound as a light oil in (42.5 g, 0.14 mol, 74%).

後処理

  1. stirringthe latter was stirred for 15 min
  2. temperaturethe reaction mixture was refluxed for 3 h
  3. temperatureThe mixture was cooled
  4. customThe organic layer was separated
  5. washwashed with water (2×100 mL)
  6. extractionThe combined aqueous layer was extracted with ethyl acetate/hexane (3:1) mixture (2×200 mL)
  7. filtrationThe organic layers were sequentially filtered through silica (25 g; 63-100 μm) and sodium sulphate (50 g)
  8. customevaporated
  9. additionThe fractions, containing the product
  10. customwere collected
  11. customevaporated

出典と根拠

ORDレコード
ord-43b944905330428d9fa1956a45deeee2
出典データセット
uspto-grants-2014_06
特許番号
US08741934B2

関連ノート

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