2-Oxo-4-phenylbutyric acid → HCID 18605781, compound
Reaction equation
O=[C:2]([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3]([OH:5])=[O:4].[NH2:14][C@H:15]1[CH2:21][CH2:20][CH2:19][CH2:18][N:17]([CH:22]([C:33]([OH:35])=[O:34])[CH2:23][C:24]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[NH:26][CH:25]=2)[C:16]1=[O:36].C([BH3-])#N.[Na+]>>[C:33]([CH:22]([N:17]1[CH2:18][CH2:19][CH2:20][CH2:21][C@H:15]([NH:14][CH:2]([C:3]([OH:5])=[O:4])[CH2:6][CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:16]1=[O:36])[CH2:23][C:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[NH:26][CH:25]=1)([OH:35])=[O:34]Participants
Procedure
Methyl 3-[3-indolyl]-2-oxopropionate (1.09 g) and α-t-Boc-L-lysine (0.246 g) are dissolved in ethanol solvent containing powdered 4 Å molecular sieves (1.87 g). A solution of sodium cyanoborohydride (0.189 g) in ethanol is added at room temperature over six hours. When reaction is complete, the solvent is removed and the residue is partitioned between ether and water. The aqueous layer is isolated and pH adjusted to 3.6. The crude product is extracted into ethyl acetate and purified by LH-20 chromatography. Ring closure to 3-(S)-t-butoxycarbonylamino-1-[1-carbomethoxy-2-(3-indolyl)ethyl]perhydroazepin-2-one is carried out as described in Example 3. Saponification of the methyl ester and subsequent formic acid treatment to remove the t-butoxycarbonyl protecting group yields 3-(S) -amino-1-[1-carboxy-2-(3-indolyl)ethyl]perhydroazepin-2-one. 2-Oxo-4-phenylbutyric acid and this caprolactam are condensed in the presence of sodium cyanoborohydride to yield 1-[1-carboxy-2-(3-indolyl)ethyl]-3-(S)-[(1-carboxy-3-phenylpropyl)amino]perhydroazepin-2-one. The silylated mass spectrum shows a parent ion at 693 m/e [3TMS+477 MWt], and loss of CH3 =678 m/e is observed.
Sources & evidence
- ORD record
- ord-fbe94e356c094408a5725a58a5523201
- Source dataset
- uspto-grants-1987_07
- Patent number
- US04680392
Reaction notes
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