Lithium Hydroxide → 5-(((tert-butoxy)carbonyl)amino)-1H-indole-2-carboxylic acid
Reaction equation
[C:1]([N:8]1[C:16]2[C:11](=C[C:13]([NH2:17])=[CH:14][CH:15]=2)C=C1C(OC)=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Li+].[OH-:23].[CH2:24]1[CH2:28][O:27][CH2:26][CH2:25]1.CO.O>>[C:4]([O:3][C:1]([NH:8][C:16]1[CH:11]=[C:28]2[C:13](=[CH:14][CH:15]=1)[NH:17][C:25]([C:26]([OH:23])=[O:27])=[CH:24]2)=[O:2])([CH3:7])([CH3:6])[CH3:5]Participants
Conditions
- Temperature
- 60 °C
Procedure
A solution of N—BOC-5-amino-2-(methoxycarbonyl)indole (57 mg, 0.2 mmol, 1.0 equiv) in THF—CH3OH—H2O (2.4 mL) was treated with aqueous 1 N LiOH (0.24 mL, 0.24 mmol, 1.2 equiv). The reaction mixture was warmed at 60° C. for 2 h. The solvent was concentrated under a N2 stream and H2O (3 mL) was added. This solution was treated with 10% aqueous HCl until the mixture was acidic. The insoluble solid was collected by centrifugation and washed with H2O (2×3 mL). Drying the solid afforded the title compound (53 mg, 96%) as a white solid: mp 235-250° C. (decomp.); 1H NMR (acetone-d6, 400 MHz) δ 10.74 (br s, 1H, COOH), 8.26 (br s, 1H, NH), 7.95 (br s, 1H, NH), 7.43 (d, 1H, J=8.9 Hz, C6-H), 7.42 (s, 1H, C3-H), 7.39 (dd, 1H, J=8.9, 1.9 Hz, C7-H), 7.13 (dd, 1H, J=2.1, 0.8 Hz, C4-H), 1.49 (s, 9H, C(CH3)3); IR (neat) νmax 3351, 1698, 1536, 1236, 1177 cm−1; FABHRMS (NBA-NaI) m/z 299.1003 (M++Na, C14H16N2O4 requires 299.1008).
Workup
- concentrationThe solvent was concentrated under a N2 stream and H2O (3 mL)
- additionwas added
- additionThis solution was treated with 10% aqueous HCl until the mixture
- customThe insoluble solid was collected by centrifugation
- washwashed with H2O (2×3 mL)
- customDrying the solid
Sources & evidence
- ORD record
- ord-ed0fafb8db4640aab9f746f54f0ead9d
- Source dataset
- uspto-grants-2001_08
- Patent number
- US06281354B1
Reaction notes
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