Water → HCID 46737468, compound

HRID 625869Notes

Reaction equation

HRID 625869 reaction equation
C([O:8][C:9]([N:11]([CH3:25])[C@H:12]([CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]([OH:15])=[O:14])=O)C1C=CC=CC=1.O.C1C(=O)N(OC([O:37][CH2:38][CH:39]2[C:51]3[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=3)[C:45]3[C:40]2=[CH:41][CH:42]=[CH:43][CH:44]=3)=O)C(=O)C1>CO.C(#N)C.CCOC(C)=O.[Pd]>[CH:50]1[C:51]2[CH:39]([CH2:38][O:37][C:9]([N:11]([CH3:25])[C@H:12]([CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[C:13]([OH:15])=[O:14])=[O:8])[C:40]3[C:45](=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:46]=2[CH:47]=[CH:48][CH:49]=1

Participants

8

Reactant 3

HCID 962WaterHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 90457331HCID 90457331, compound

Product 1

HCID 46737468HCID 46737468, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-2-(((benzyloxy)carbonyl)(methyl)amino)-5-(tert-butoxy)-5-oxopentanoic acid (1.40 g, 3.98 mmol) in MeOH (18.79 ml) was added 10% Pd/C (0.424 g, 0.398 mmol) and the reaction mixture was placed under a hydrogen atmosphere using. The reaction was allowed to stir at room temperature for 18 h. The catalyst was removed by filtration on CELITE® and the filtrate was concentrated under reduced pressure to give a white solid. The crude material was dissolved in Acetonitrile (9.40 ml), Water (9.40 ml) and TEA (1.111 mL, 7.97 mmol). The solution was cooled to 0° C. using and icebath and the FMOC-OSU (1.344 g, 3.98 mmol) was added. The reaction mixture was allowed to stir while warming up to room temperature for 18 hours. The crude product was diluted in 200 mL EtOAc and washed with 1N HCl aqueous solution and brine. The organic phase was dried over anhydrous sodium sulfate. After filtration and concentration a clear oil was obtained, which was purified by silica gel chromatography using 100% hexanes to 100% EtOAc. (R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-5-(tert-butoxy)-5-oxopentanoic acid was obtained as a colorless oil (0.481 g, 28%). 1H NMR (400 MHz, chloroform-d) δ 7.81-7.68 (m, 2H), 7.63-7.49 (m, 2H), 7.43-7.21 (m, 4H), 5.95 (br. s., 3H), 4.76 (dd, J=10.7, 4.5 Hz, 1H), 4.60-4.48 (m, 1H), 4.47-4.32 (m, 2H), 4.29-4.10 (m, 1H), 2.87 (s, 3H), 2.43-1.82 (m, 4H), 1.51-1.36 (m, 9H).

Workup

  1. customThe catalyst was removed by filtration on CELITE®
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customto give a white solid
  4. temperatureThe solution was cooled to 0° C.
  5. stirringto stir
  6. temperaturewhile warming up to room temperature for 18 hours
  7. washwashed with 1N HCl aqueous solution and brine
  8. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  9. filtrationAfter filtration and concentration a clear oil
  10. customwas obtained
  11. customwhich was purified by silica gel chromatography

Sources & evidence

ORD record
ord-b6d0915942594795b7455ee126733ba1
Source dataset
uspto-grants-2016_04
Patent number
US09308236B2

Reaction notes

Loading…