Potassium Carbonate → (s)-methyl 2-(benzyloxycarbonylamino)-3-((1r*,3R*,4R*)-3-fluoro-4-hydroxycyclopentyl)propanoate

HRID 451806Notes

Reaction equation

HRID 451806 reaction equation
[Si]([O:8][C@H:9]1[C@H:13]([F:14])[CH2:12][C@H:11]([CH2:15][C@H:16]2[C:21]([O:22][CH3:23])=N[C@H](C(C)C)C(OC)=[N:17]2)[CH2:10]1)(C(C)(C)C)(C)C.C([O-])([O-])=[O:30].[K+].[K+].[C:35]([O:45]N1C(=O)CCC1=O)([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=O>Cl.C(#N)C.O>[CH2:38]([O:37][C:35]([NH:17][C@@H:16]([CH2:15][C@@H:11]1[CH2:10][C@@H:9]([OH:8])[C@H:13]([F:14])[CH2:12]1)[C:21]([O:22][CH3:23])=[O:30])=[O:45])[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 83172Benzyl succinimido carbonateHCID 59201654(2S,5R)-2-(((1r*,3R*,4R*)-3-(tert-butyldimethylsilyloxy)-4-fluorocyclopentyl)methyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine

Product 1

HCID 59201738(s)-methyl 2-(benzyloxycarbonylamino)-3-((1r*,3R*,4R*)-3-fluoro-4-hydroxycyclopentyl)propanoateYield 67%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

(2S,5R)-2-(((1r*,3R*,4R*)-3-(tert-butyldimethylsilyloxy)-4-fluorocyclopentyl)methyl)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (500 mg, 1.21 mmol) was dissolved in 1:1 mixture of 1 N HCl solution and acetonitrile (50 mL). The mixture was stirred 3 h at rt, then concentrated. K2CO3 (840 mg, 5 equiv.) and CbzOSu (903 mg, 3 equiv.) were added to the residue, The mixture was dissolved in 1:1 water and acetonitrile (50 mL), stirred overnight at rt. The acetonitrile was removed by evaporation under reduced pressure. The aqueous residue was extracted by EtOAc (3×20 mL). The combined organic layers were washed by brine (20 mL), dried over Na2SO4. After filtration and concentration, the residue was purified by ISCO (40 g column) to afford 274 mg (67% yield) of (s)-methyl 2-(benzyloxycarbonylamino)-3-((1r*,3R*,4R*)-3-fluoro-4-hydroxycyclopentyl)propanoate. MS ESI +ve m/z 362 (M+Na). 1H NMR (CDCl3) δ 7.35 (m, 5H), 5.34 (s, 1H), 5.10 (s, 2H), 4.82 (d, 1H), 4.39-4.19 (m, 2H), 3.73 (s, 3H), 2.43-2.24 (m, 2H), 2.09-1.38 (m, 6H). 19F NMR (CDCl3) δ −175.92.

Workup

  1. concentrationconcentrated
  2. stirringstirred overnight at rt
  3. customThe acetonitrile was removed by evaporation under reduced pressure
  4. extractionThe aqueous residue was extracted by EtOAc (3×20 mL)
  5. washThe combined organic layers were washed by brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration and concentration
  8. customthe residue was purified by ISCO (40 g column)

Sources & evidence

ORD record
ord-cb14acf4c2064aebba476cad7b42deb1
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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