3-Hydroxy-2,2-dimethylpropionic acid → HCID 86692262、化合物

HRID 1469785ノート

反応式

HRID 1469785 の反応式
[NH2:1][CH2:2][C:3]1[C:4]([F:15])=[C:5]([C:11]([Cl:14])=[CH:12][CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7].[OH:16][CH2:17][C:18]([CH3:23])([CH3:22])[C:19](O)=[O:20].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:14][C:11]1[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:4]([F:15])[C:3]([CH2:2][NH:1][C:17](=[O:16])[C:18]([CH3:23])([CH3:22])[CH2:19][OH:20])=[CH:13][CH:12]=1

参加物

7

反応物 4

HCID 785483-Hydroxy-2,2-dimethylpropionic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 58483233Ethyl 3-(aminomethyl)-6-chloro-2-fluorobenzoate

生成物 1

HCID 86692262HCID 86692262、化合物収率 61.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of ethyl 3-(aminomethyl)-6-chloro-2-fluorobenzoate (Intermediate-2, step-1, 800 mg, 3.45 mmol) and 3-hydroxy-2,2-dimethylpropanoic acid (591 mg, 5.00 mmol) in DMF (5 mL) were added (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (2.29 g, 5.18 mmol) and DIPEA (1.29 g, 10.0 mmol). Then reaction mixture was stirred at rt for 12 h and it was diluted with EtOAc, washed with H2O and brine. The organic layer was separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 700 mg of the title product. 1H NMR (400 MHz, DMSO d6): δ 8.09-8.06 (t, J=8.0 Hz, 1H), 7.45-7.38 (m, 2H), 4.91-4.88 (t, J=5.2 Hz, 1H), 4.42-4.37 (q, J=8.0 Hz, 2H), 4.29-4.28 (d, J=5.6 Hz, 2H), 3.48 (m, 2H), 1.33-1.29 (t, J=8.0 Hz, 3H), 1.05 (s, 6H).

後処理

  1. customThen reaction mixture
  2. washwashed with H2O and brine
  3. customThe organic layer was separated
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography

出典と根拠

ORDレコード
ord-2e199219227b4aa9b768a8ea39838352
出典データセット
uspto-grants-2015_04
特許番号
US09006257B2

反応ノート

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