Sodium Carbonate → HCID 68284530, compound

HRID 1527407Notes

Reaction equation

HRID 1527407 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([N:13]=[N+]=[N-])[C@H:10]([O:16][CH3:17])[C@H:9]1[C:18]([O:20]CC1C=CC=CC=1)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].[C:34](ON1C(=O)CCC1=O)([O:36][CH2:37][CH:38]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[C:44]2[C:39]1=[CH:40][CH:41]=[CH:42][CH:43]=2)=[O:35].[NH4+].[Cl-].[Cl:61][C:62]1[C:63]([F:70])=[C:64]([CH:67]=[CH:68][CH:69]=1)[CH2:65][NH2:66].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO.[Pd].C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([NH:13][C:34]([O:36][CH2:37][CH:38]2[C:50]3[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=3[C:44]3[C:39]2=[CH:40][CH:41]=[CH:42][CH:43]=3)=[O:35])[C@H:10]([O:16][CH3:17])[C@H:9]1[C:18](=[O:20])[NH:66][CH2:65][C:64]1[CH:67]=[CH:68][CH:69]=[C:62]([Cl:61])[C:63]=1[F:70])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

12

Reactant 7

HCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2773614(3-Chloro-2-fluorophenyl)methanamineHCID 131733205HCID 131733205, compound

Product 1

HCID 68284530HCID 68284530, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (2S,3R,4R)-4-azido-3-methoxy-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (440 mg, 1.16 mmol) in methanol (3 mL) was hydrogenated with palladium on carbon 10% (124 mg, 1.16 mmol) overnight. The reaction mixture was filtered over a glass fiber filter, washed with methanol and evaporated in vacuo. The residue was dissolved in THF (2 mL) and a 10% aqueous Na2CO3 (3.09 mL, 1.11 mmol) solution was added. The reaction mixture was cooled at 0° C. then FmocOSu dissolved in THF (7 mL) was added and stirred for 2 h at RT. The reaction mixture was concentrated in vacuo to leave a residue which was dissolved in EtOAc (10 mL) and treated with saturated aq. NH4Cl solution. The mixture was extracted with EtOAc (3×20 mL) and the organic layers were collected, dried over MgSO4, filtered and concentrated. The residue was dissolved in DMF (3 mL) then 3-chloro-2-fluoro benzylamine (267 mg, 1.67 mmol) and HBTU (526 mg, 1.38 mmol), DIPEA (292 μl, 1.67 mmol) were added. The resulting orange solution was stirred overnight at RT. Purification by flash column chromatography on silica gel (c-hexane/EtOAc 3:2) afforded the title compound. MS (UPLC/MS): 624/626 [M+H]+, 668/670 [M+HCOO]−; tR (HPLC conditions f): 2.65 min.

Workup

  1. filtrationThe reaction mixture was filtered over a glass fiber
  2. filtrationfilter
  3. washwashed with methanol
  4. customevaporated in vacuo
  5. dissolutionThe residue was dissolved in THF (2 mL)
  6. additionwas added
  7. concentrationThe reaction mixture was concentrated in vacuo
  8. customto leave a residue which
  9. extractionThe mixture was extracted with EtOAc (3×20 mL)
  10. customthe organic layers were collected
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. dissolutionThe residue was dissolved in DMF (3 mL)
  15. stirringThe resulting orange solution was stirred overnight at RT
  16. customPurification by flash column chromatography on silica gel (c-hexane/EtOAc 3:2)

Sources & evidence

ORD record
ord-716bbef63d174dc7838a27545285c79a
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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