methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate → (S)-2-(Tert-butoxycarbonylamino)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)phenyl]propanoic acid

HRID 215938ノート

反応式

HRID 215938 の反応式
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([B:21]2[O:25][C:24]([CH3:27])([CH3:26])[C:23]([CH3:29])([CH3:28])[O:22]2)=[CH:17][CH:16]=1)[C:10]([O:12]C)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].B(C1C=CC(C[C@H](NC(OC(C)(C)C)=O)C(O)=O)=CC=1)(O)O>>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:16]=[CH:17][C:18]([B:21]2[O:25][C:24]([CH3:27])([CH3:26])[C:23]([CH3:29])([CH3:28])[O:22]2)=[CH:19][CH:20]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

3

反応物 2

HCID 10949509methyl (2S)-2-{[(tert-butoxy)carbonyl]amino}-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoateHCID 58746869[(S)-3-(4-boronophenyl)-2-((tertbutoxycarbonyl)amino)propanoic acid]

生成物 1

HCID 10644158(S)-2-(Tert-butoxycarbonylamino)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)phenyl]propanoic acid

実験手順

The above organic layer of the ester was stirred with aqueous lithium hydroxide solution (23 g in 500 mL water) at room temperature for 30 minutes. The pH of the resulting slurry was adjusted to about 10 with 6 N hydrochloric acid and filtered. The cake was washed with water (200 mL). Acetonitrile was removed from the filtrate under reduced pressure to give an aqueous slurry (950 mL, additional water was added during distillation). The slurry was filtered through a pad of cellulose and washed with water (200 mL). The filtrate was washed with MTBE (500 mL) and rediluted with 700 mL MTBE. The mixture was acidified to pH about 4.5 with 6 N hydrochloric acid. The organic layer was washed with water (500 mL) and concentrated under reduced pressure to the acid compound as a brown oil (206 g, 95% yield based on estimated purity by NMR). The crude product can be used directly in the following step. Alternatively, the compound can be purified by crystallization from MTBE/heptane to give a white solid, which contains a small amount of the corresponding boronic acid, (S)-3-(4-boronophenyl)-2-(tert-butoxycarbonylamino)propanoic acid. MS (ESI): MH+=392.2, MNH4+=409.2, M2H+=783.4, M2NH4+=800.4. 1H NMR (CDCl3) δ 7.95 (br s, 1H), 7.76 (d, J=7.8 Hz, 2H), 7.21 (d, J=7.6 Hz, 2H), 5.03 (d, J=7.8 Hz, 1H), 4.62 (m, 1H), 3.18 (m, 2H), 1.43 (s, 9H), 1.35 (s, 12H). 13C NMR (CDCl3) δ 175.8, 155.7, 139.7, 135.4, 129.2, 84.2, 80.5, 54.5, 38.3, 28.7, 25.2.

後処理

  1. customAlternatively, the compound can be purified by crystallization from MTBE/heptane
  2. customto give a white solid, which

出典と根拠

ORDレコード
ord-bd986a8bfe46489bbb7e76e21c5cfd27
出典データセット
uspto-grants-2012_06
特許番号
US08193204B2

反応ノート

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