Ammonium Chloride → (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-carbamoyl-2,6-dimethylphenyl)propanoate

HRID 1620135ノート

反応式

HRID 1620135 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:22]([O:24][CH3:25])=[O:23])[CH2:10][C:11]1[C:19]([CH3:20])=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][C:12]=1[CH3:21])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C[N:29]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH4+].[Cl-]>CN(C=O)C>[CH3:25][O:24][C:22](=[O:23])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:10][C:11]1[C:19]([CH3:20])=[CH:18][C:14]([C:15](=[O:16])[NH2:29])=[CH:13][C:12]=1[CH3:21]

参加物

7

反応物 5

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 58631279(S)-4-(2-tert-Butoxycarbonylamino-2-methoxycarbonylethyl)-3,5-dimethylbenzoic acid

生成物 1

HCID 58631271(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-carbamoyl-2,6-dimethylphenyl)propanoate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Into a stirring solution of (S)-4-(2-tert-butoxycarbonylamino-2-methoxycarbonylethyl)-3,5-dimethylbenzoic acid (3.00 g, 8.54 mmol), PyBOP (6.68 g, 12.8 mmol) and HOBt (1.74 g, 12.8 mmol) in DMF (36 mL) was added DIPEA (5.96 mL, 34.2 mmol) and NH4Cl (0.92 g, 17.1 mmol). The resulting mixture was stirred at rt for 40 min before being partitioned between aqueous NH4Cl solution and EtOAc. The separated organic phase was washed sequentially with 2N citric acid aqueous solution, saturated aqueous NaHCO3 solution, and brine, then dried over Na2SO4 overnight. After filtration and concentration, the residue was purified by flash column chromatography (eluent: EtOAc) to give the product. (3.00 g, 100%); 1H NMR (300 MHz, CDCl3): δ 1.36 (9H, s), 2.39 (6H, s), 3.11 (2H, J=7.2 Hz), 3.65 (3H, s), 4.53-4.56 (1H, m), 5.12 (1H, d, J=8.7 Hz), 5.65 (1H, br s), 6.09 (1H, br s), 7.46 (2H, s); MS (ES+) (relative intensity): 250.9 (100) (M-Boc)+.

後処理

  1. custombefore being partitioned between aqueous NH4Cl solution and EtOAc
  2. washThe separated organic phase was washed sequentially with 2N citric acid aqueous solution, saturated aqueous NaHCO3 solution, and brine
  3. dry with materialdried over Na2SO4 overnight
  4. filtrationAfter filtration and concentration
  5. customthe residue was purified by flash column chromatography (eluent: EtOAc)
  6. customto give the product

出典と根拠

ORDレコード
ord-e72dc4cf427e46e4be42d0329ecbaa6b
出典データセット
uspto-grants-2014_07
特許番号
US08772325B2

反応ノート

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