Triethylamine → [(RS)-1-(6-Bromo-pyridin-2-yl)-2-((R)-1-cyano-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-carbamic acid tert-butyl ester

HRID 538315ノート

反応式

HRID 538315 の反応式
[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Br:27])[N:22]=1)([CH3:20])[CH2:9][O:10][C@@:11]([C:17](=O)[NH2:18])([CH3:16])[C:12]([F:15])([F:14])[F:13])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.N.CO>C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]([C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Br:27])[N:22]=1)([CH3:20])[CH2:9][O:10][C@@:11]([C:17]#[N:18])([CH3:16])[C:12]([F:14])([F:15])[F:13])([CH3:2])([CH3:3])[CH3:4]

参加物

7

反応物 4

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 21705897Ammonia methanolHCID 86715546[(RS)-1-(6-Bromo-pyridin-2-yl)-2-((R)-1-carbamoyl-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-carbamic acid tert-butyl ester

生成物 1

HCID 86715548[(RS)-1-(6-Bromo-pyridin-2-yl)-2-((R)-1-cyano-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-carbamic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 10340Sodium Carbonate溶媒

反応条件

温度
0 °C

実験手順

To an at 0° C. per cooled solution of [(RS)-1-(6-bromo-pyridin-2-yl)-2-((R)-1-carbamoyl-2,2,2-trifluoro-1-methyl-ethoxy)-1-methyl-ethyl]-carbamic acid tert-butyl ester (2.18 g, 4.64 mmol) and NEt3 (1.615 ml, 1.173 g, 11.59 mmol) in DCM (30 ml) was added dropwise TFAA (0.773 ml, 1.168 g, 5.56 mmol). After stirring for 5 min at 0° C., then for 1 h at rt the reaction mixture was diluted with sat. aq. Na2CO3 soln. and with DCM. The phases were separated and the aq. phase was twice reextracted with DCM. The combined org. phases were dried over Na2SO4, filtered and concentrated to leave a pale yellow oil which was stirred with 7N NH3/MeOH for 5 min. The mixture was evaporated to dryness and purified by flash chromatography (cyclohexane: EtOAc 0-3 min 100:0, 3-35 min 65:35) to yield the title compound as a clear oil.

後処理

  1. customThe phases were separated
  2. dry with materialphases were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto leave a pale yellow oil which
  6. customThe mixture was evaporated to dryness
  7. custompurified by flash chromatography (cyclohexane: EtOAc 0-3 min 100:0, 3-35 min 65:35)

出典と根拠

ORDレコード
ord-68b2254f6ed347bbb1d52abff396f6ed
出典データセット
uspto-grants-2014_10
特許番号
US08865712B2

反応ノート

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