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

HRID 1443385ノート

反応式

HRID 1443385 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 stirrng solution of the benzoic acid from Step B (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 with 2 N citric acid aqueous solution, saturated aqueous NaHCO3 solution and brine, and dried over Na2SO4 overnight. After concentration, the residue was purified by flash column chromatography (eluent: EtOAc) to give the title amide. 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 with 2 N citric acid aqueous solution, saturated aqueous NaHCO3 solution and brine
  3. dry with materialdried over Na2SO4 overnight
  4. concentrationAfter concentration
  5. customthe residue was purified by flash column chromatography (eluent: EtOAc)

出典と根拠

ORDレコード
ord-85265df67a084e88a612487527b75e9f
出典データセット
uspto-grants-2010_02
特許番号
US07659402B2

反応ノート

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