Chloroacetic Acid → (2R,3R)-3-(2-Chloro-acetoxy)-2-((S)-7-cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 449829ノート

反応式

HRID 449829 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([OH:13])[C@H:9]1[CH2:14][N:15]1[C:23]2[CH:22]=[CH:21][C:20]([C:24]#[N:25])=[CH:19][C:18]=2[C:17]2[CH2:26][C@H:27]([NH:29][C:30]([O:32][CH:33]([CH3:35])[CH3:34])=[O:31])[CH2:28][C:16]1=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:36][CH2:37][C:38](O)=[O:39].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([O:13][C:38](=[O:39])[CH2:37][Cl:36])[C@H:9]1[CH2:14][N:15]1[C:23]2[CH:22]=[CH:21][C:20]([C:24]#[N:25])=[CH:19][C:18]=2[C:17]2[CH2:26][C@H:27]([NH:29][C:30]([O:32][CH:33]([CH3:35])[CH3:34])=[O:31])[CH2:28][C:16]1=2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 300Chloroacetic AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 66933249(2R,3S)-2-((S)-7-Cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 86651083(2R,3R)-3-(2-Chloro-acetoxy)-2-((S)-7-cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester収率 54%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture of (2R,3S)-2-((S)-7-cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (950 mg, 1.97 mmol), chloroacetic acid (227 mg, 2.36 mmol), and triphenylphosphine (626 mg, 2.36 mmol) in tetrahydrofuran (20 mL) is treated with diethyl azodicarboxylate (374 μL, 2.36 mmol) dropwise at room temperature. The reaction mixture is stirred overnight. The reaction is diluted with ethyl acetate (50 mL) and then washed with water and brine. The organic portion is dried over sodium sulfate and concentrated. The resulting residue is purified by medium pressure liquid chromatography, eluting with ethyl acetate:hexane (1:1). Fractions containing pure product are combined and concentrated to afford 0.59 g (54%) of the title compound. LC-ES/MS m/z 581.0 [M+Na]+, TR=4.46 min.

後処理

  1. washwashed with water and brine
  2. dry with materialThe organic portion is dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe resulting residue is purified by medium pressure liquid chromatography
  5. washeluting with ethyl acetate:hexane (1:1)
  6. additionFractions containing pure product
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-90fcf7ab9c5344a5b8b86ce11469e227
出典データセット
uspto-grants-2013_07
特許番号
US08486943B2

反応ノート

読み込み中…