Hydrochloric Acid → (3R)-1-Amino-3-(4-bromophenyl)cyclopentanecarboxylic acid
Reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:18][CH2:17][C:10]3([NH:14]C(=O)N[C:11]3=[O:16])[CH2:9]2)=[CH:4][CH:3]=1.[OH-:19].[Na+].Cl>O1CCOCC1>[NH2:14][C:10]1([C:11]([OH:19])=[O:16])[CH2:17][CH2:18][C@@H:8]([C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=2)[CH2:9]1Participants
Procedure
A solution of (7R)-7-(4-bromophenyl)-1,3-diazaspiro[4.4]nonane-2,4-dione (I-2B, 6.80 g, 22 mmol) in dioxane (20 mL) and NaOH (2N aq) (120 mL, 240 mmol) was heated in an oil bath set to 95° C. The resulting clear, pale yellow solution was left to stir over the weekend. The solution was cooled in an ice bath and neutralized to approximately pH 7 with 6 N HCl resulting in the formation of a precipitate. The solids were collected and left to air dry overnight. The white solid was slurried in hot ethanol (˜100 mL) and re-collected by filtration and the solid was air-dried then placed under high vacuum. (5.8 g, 20.41 mmol). HPLC retention time=0.64 min (Condition G); LC/MS M+1=284/286. 1H NMR (500 MHz, methanol-d4) δ 7.52-7.38 (m, 2H), 7.31-7.17 (m, 2H), 3.55-3.40 (m, 1H), 2.68 (dd, J=13.3, 6.7 Hz, 1H from single diastereomer), 2.58-2.39 (m, 1H), 2.26-2.15 (m, 1H), 2.10-1.98 (m, 1H), 1.98-1.81 (m, 1H), 1.70 (dd, J=13.2, 11.8 Hz, 1H from single diastereomer).
Workup
- customset to 95° C
- waitThe resulting clear, pale yellow solution was left
- customThe solids were collected
- waitleft to air
- customdry overnight
- filtrationre-collected by filtration
- customthe solid was air-dried
Sources & evidence
- ORD record
- ord-e79fff06a20548099809a2610a1021b9
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09115054B2
Reaction notes
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