Citric Acid → (r)-2-[2-(Tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid sodium salt
Reaction equation
C1(N)CCCCC1.[C:8]([O:12][C:13](=[O:28])[CH2:14][C@@H:15]([CH2:19][CH2:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]([OH:18])=[O:17])([CH3:11])([CH3:10])[CH3:9].C(OCC)(=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[OH-].[Na+:49]>O>[Na+:49].[C:8]([O:12][C:13](=[O:28])[CH2:14][C@@H:15]([CH2:19][CH2:20][CH2:21][CH:22]1[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1)[C:16]([O-:18])=[O:17])([CH3:11])([CH3:9])[CH3:10]Participants
Procedure
(R)-2-[2-(tert-Butoxy)-2-oxoethyl]-5-phenylpentanoic acid cyclohexylamine salt (Preparation 166, 6.8 g, 17 mmol) and ethyl acetate (100 ml) were added to an aqueous solution of citric acid (10%, 100 ml) and the organic phase was separated and washed with water (100 ml). Iso-propyl alcohol (20 ml) and 5% rhodium on alumina (51.6 g) were added and the mixture was stirred at room temperature, under hydrogen (10 atmospheres, 150 p.s.i.) for 48 hours and then filtered through celite. To the filtrate was added a solution of sodium hydroxide (0.67 g, 17 mmol) in water and the mixture was stripped and replaced with acetonitrile by distillation at atmospheric pressure to a volume of 30 ml. The mixture was allowed to cool to room temperature where it was stirred for 24 hours. The mixture was cooled to 0° C. and then filtered. The residue was washed with acetonitrile (2×10 ml) and then dried in vacuo at 45° C. for 2 hours to leave the title compound as a colourless solid (3.8 g, 69% yield, 95% pure by NMR).
Workup
- customthe organic phase was separated
- washwashed with water (100 ml)
- additionIso-propyl alcohol (20 ml) and 5% rhodium on alumina (51.6 g) were added
- filtrationfiltered through celite
- distillationreplaced with acetonitrile by distillation at atmospheric pressure to a volume of 30 ml
- temperatureto cool to room temperature where it
- stirringwas stirred for 24 hours
- temperatureThe mixture was cooled to 0° C.
- filtrationfiltered
- washThe residue was washed with acetonitrile (2×10 ml)
- customdried in vacuo at 45° C. for 2 hours
Sources & evidence
- ORD record
- ord-ef21f940009c42c4986284ee8399454e
- Source dataset
- uspto-grants-2004_04
- Patent number
- US06716861B2
Reaction notes
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