Triethylamine → (2R,5R)-5-(6-bromo-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

HRID 474107ノート

反応式

HRID 474107 の反応式
[Br:1][C:2]1[N:7]=[C:6]([C@:8]([NH:21]S(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)([CH3:20])[CH2:9][O:10][C@@:11]([CH3:19])([C:15]([F:18])([F:17])[F:16])[C:12]([NH2:14])=O)[C:5]([F:34])=[CH:4][CH:3]=1.C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)Cl>[Br:1][C:2]1[N:7]=[C:6]([C@:8]2([CH3:20])[CH2:9][O:10][C@@:11]([CH3:19])([C:15]([F:18])([F:17])[F:16])[C:12]([NH2:14])=[N:21]2)[C:5]([F:34])=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 8471Triethylamine2 回HCID 9845Trifluoroacetic anhydride2 回HCID 86668077(R)-2-[(R)-2-(6-Bromo-3-fluoro-pyridin-2-yl)-2-(4-nitro-benzenesulfonylamino)-propoxy]-3,3,3-trifluoro-2-methyl-propionamide

生成物 1

HCID 86668039(2R,5R)-5-(6-bromo-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine収率 148.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
2.5 °C

実験手順

A suspension of (R)-2-[(R)-2-(6-bromo-3-fluoro-pyridin-2-yl)-2-(4-nitro-benzenesulfonylamino)-propoxy]-3,3,3-trifluoro-2-methyl-propionamide (8.43 g, 14.70 mmol) and triethylamine (5.12 ml, 36.8 mmol) in 85 ml DCM was cooled to 0-5° C. Trifluoroacetic anhydride (2.49 ml, 17.64 mmol) was added dropwise over 30 min. Additional triethylamine (1.54 ml, 11.07 mmol) and trifluoroacetic anhydride (0.75 ml, 5.29 mmol) were added to complete the reaction. The reaction mixture was quenched by addition of 14 ml aqueous ammonia (25%) and 14 ml water. The emulsion was stirred for 15 min, more water and DCM were added and the layers were separated. The organic layer was dried with MgSO4 H2O, filtered and evaporated. Purification by column chromatography on a silica gel (hexanes/10-25% EtOAc) gave 8.09 g of the title compound as a yellow resin.

後処理

  1. customthe reaction
  2. customThe reaction mixture was quenched by addition of 14 ml aqueous ammonia (25%) and 14 ml water
  3. additionmore water and DCM were added
  4. customthe layers were separated
  5. dry with materialThe organic layer was dried with MgSO4 H2O
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by column chromatography on a silica gel (hexanes/10-25% EtOAc)

出典と根拠

ORDレコード
ord-6d652aedb6f546f3a7955f2460a84b8c
出典データセット
uspto-grants-2014_01
特許番号
US08637508B2

反応ノート

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