Diethyl Ether → N-Boc-Tyr(Bn)-Ala-Trp-OH

HRID 2074365ノート

反応式

HRID 2074365 の反応式
[NH:1]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[C@H:2]([C:18]([NH:20][C@H:21]([C:23]([NH:25][C@H:26]([C:37]([O:39]C)=[O:38])[CH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)=[O:24])[CH3:22])=[O:19])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:6][CH:5]=1.[Li+].[OH-].C1(NC2CCCCC2)CCCCC1.CCOCC>C1COCC1.CO>[NH:1]([C:41]([O:43][C:44]([CH3:45])([CH3:47])[CH3:46])=[O:42])[C@H:2]([C:18]([NH:20][C@H:21]([C:23]([NH:25][C@H:26]([C:37]([OH:39])=[O:38])[CH2:27][C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[NH:30][CH:29]=1)=[O:24])[CH3:22])=[O:19])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:6][CH:5]=1

参加物

7

反応物 4

HCID 3283Diethyl EtherHCID 3939Lithium HydroxideHCID 7582DicyclohexylamineHCID 44424692N-Boc-Tyr(Bn)-Ala-Trp-OMe

生成物 1

HCID 44424695N-Boc-Tyr(Bn)-Ala-Trp-OH収率 64%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

compound NR66. Saponification of N-Boc-Tyr(Bn)-Ala-Trp-OMe (580 mg, 0.902 mmol) in THF (5 mL) by 1 M aqueous LiOH (2 mL, 2 mmol) at 4° C. for 1 hour, afforded after acidic treatment and precipitation of the residue with water crude N-Boc-Tyr(Bn)-Gly-Trp-OH. The crude product in MeOH (0.5 mL) was treated by dicyclohexylamine (0.18 mL, 0.91 mmol) and then ether (10 mL). After filtration, the resulting solid was dissolved in CH2Cl2 (10 mL) and washed by 10% aqueous citric acid. The organic phase was dried over MgSO4 and concentrated to afford N-Boc-Tyr(Bn)-Ala-Trp-OH (361 mg, 64%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 1.20 (d, J=7 Hz, 3H, CH3), 1.28 (s, 9H, (CH3)3), 2.62 and 2.86 (ABX system, 2H, CH2β), 3.09 and 3.18 (ABX system, 2H, CH2β), 4.10 (m, 1H, CHα), 4.35 (m, 1H, CHα), 4.46 (m, 1H, CHα), 5.03 (s, 2H, CH2 (OBn)), 6.87-7.54 (m, 15H, 14 aromatic H+1 NH), 7.96 (d, J=7.5 Hz, 1H), 8.13 (d, J=7.5 Hz, 1H), 10.84 (s, 1NH). 13C NMR (75 MHz, CDCl3) δ 18.2 (CH3), 27.2 (CH2 Trp), 28.3 ((CH3)3), 37.3 (CH2 Tyr), 48.9, 53.3, 55.7 (CHα Ala, Tyr or Trp), 70.0 (CH2 (OBn)), 80.7 (C(CH3)3), 109.5 (aromatic C), 111.5, 115.0, 118.6, 119.5, 121.9, 123.8, 127.5, 127.6, 128.1, 128.6, 130.4 (aromatic CH), 136.1, 137.0, 137.1 (aromatic C), 155.8, 157.8 (Car-O or CO carbamate), 171.9, 172.3, 174.2 (2 CO amide or CO acid). Anal. Calcd. for C35H40N4O7, 1.5H2O: C, 64.11%; H, 6.61%; N, 8.54%. Found: C, 64.19%; H, 6.36%; N, 8.79%.

後処理

  1. customafforded
  2. customafter acidic treatment and precipitation of the residue with water crude N-Boc-Tyr(Bn)-Gly-Trp-OH
  3. filtrationAfter filtration
  4. dissolutionthe resulting solid was dissolved in CH2Cl2 (10 mL)
  5. washwashed by 10% aqueous citric acid
  6. dry with materialThe organic phase was dried over MgSO4
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-3722f71ad7554e35a90b5dfcbf4e3102
出典データセット
uspto-grants-2011_04
特許番号
US07919468B2

反応ノート

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