(2R,3R)-1-benzyl 4-tert-butyl 3-(3-methylisoxazol-4-yl)-2-(3,3,3-trifluoropropyl)succinate → (R)-2-((R)-2-tert-Butoxy-1-(3-methylisoxazol-4-yl)-2-oxoethyl)-5,5,5-trifluoropentanoic acid

HRID 1771955Notes

Reaction equation

HRID 1771955 reaction equation
[CH3:1][C:2]1[C:6]([C@H:7]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@@H:8]([CH2:19][CH2:20][C:21]([F:24])([F:23])[F:22])[C:9]([O:11]CC2C=CC=CC=2)=[O:10])=[CH:5][O:4][N:3]=1.[H][H]>CO.[OH-].[OH-].[Pd+2]>[C:28]([O:27][C:25](=[O:26])[C@H:7]([C@@H:8]([CH2:19][CH2:20][C:21]([F:24])([F:22])[F:23])[C:9]([OH:11])=[O:10])[C:6]1[C:2]([CH3:1])=[N:3][O:4][CH:5]=1)([CH3:31])([CH3:29])[CH3:30]

Participants

5

Reactant 2

HCID 90079887(2R,3R)-1-benzyl 4-tert-butyl 3-(3-methylisoxazol-4-yl)-2-(3,3,3-trifluoropropyl)succinateHCID 178418361HCID 178418361, compound

Product 1

HCID 90080435(R)-2-((R)-2-tert-Butoxy-1-(3-methylisoxazol-4-yl)-2-oxoethyl)-5,5,5-trifluoropentanoic acidYield 46.9%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

In a 200 mL round-bottomed flask a colorless solution of (2R,3R)-1-benzyl 4-tert-butyl 3-(3-methylisoxazol-4-yl)-2-(3,3,3-trifluoropropyl)succinate (2.4 g, 5.44 mmol) in MeOH (Volume: 50 mL) was treated with Pearlman's Catalyst (0.076 g, 0.544 mmol) and hydrogenated using a hydrogen-filled balloon at room temperature for 1 hour until the reaction was complete (monitored by HPLC). The mixture was filtered through a 0.45 μm membrane and rinsed with MeOH. The filtrated was concentrated to give 2.03 g of crude solid. The solid was purified on Prep HPLC [C18 Luna 30×100 eluting with a gradient from 10% B to 100% B (15 min)] to afford 99% pure Intermediate (896 mg, 46% yield) as a white solid. MS(ES):m/z=352 [M+H+], m/z=350[M−H−]. 1H NMR (500 MHz, chloroform-d) δ 8.40 (s, 1H), 3.62 (d, J=10.0 Hz, 1H), 3.08 (td, J=10.0, 3.6 Hz, 1H), 2.34 (s, 3H), 2.33-2.14 (m, 2H), 2.03-1.89 (m, 2H), 1.46 (s, 9H).

Workup

  1. additionfilled balloon at room temperature for 1 hour until the reaction
  2. filtrationThe mixture was filtered through a 0.45 μm membrane
  3. washrinsed with MeOH
  4. concentrationThe filtrated was concentrated
  5. customto give 2.03 g of crude solid
  6. customThe solid was purified on Prep HPLC [C18 Luna 30×100 eluting with a gradient from 10% B to 100% B (15 min)]

Sources & evidence

ORD record
ord-15bd8aff01dc42799f5d5c93aa719ab3
Source dataset
uspto-grants-2016_02
Patent number
US09249157B2

Reaction notes

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