N-(9-Fluorenylmethoxycarbonyloxy)succinimide → ((1R,2S,3R,4R)-2,3-Dihydroxy-4-hydroxymethyl-cyclopentyl)-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 406517Notes

Reaction equation

HRID 406517 reaction equation
Cl.[OH:2][C@@H:3]1[C@H:7]([OH:8])[C@@H:6]([CH2:9][OH:10])[CH2:5][C@H:4]1[NH2:11].[CH:12]1[C:24]2[CH:23]([CH2:25][O:26][C:27](ON3C(=O)CCC3=O)=[O:28])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]=2[CH:15]=[CH:14][CH:13]=1.C(=O)([O-])O.[Na+].C(Cl)(Cl)Cl.CO.C(O)(=O)C>O.O1CCOCC1>[CH:12]1[C:24]2[CH:23]([CH2:25][O:26][C:27](=[O:28])[NH:11][C@@H:4]3[CH2:5][C@H:6]([CH2:9][OH:10])[C@@H:7]([OH:8])[C@H:3]3[OH:2])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]=2[CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 516892Sodium BicarbonateHCID 2734536(1R,2S,3R,5R)-3-amino-5-(hydroxymethyl)cyclopentane-1,2-diol HydrochlorideHCID 21866353chloroform methanol HOAc

Product 1

HCID 71623617((1R,2S,3R,4R)-2,3-Dihydroxy-4-hydroxymethyl-cyclopentyl)-carbamic acid 9H-fluoren-9-ylmethyl esterYield 95.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

(1R,2S,3R,4R)-2,3-Dihydroxy-4-(hydroxylmethyl)-1-aminocyclopentan hydro-chloride (70.0 g, 380 mmol) was dissolved in water (660 ml) and FmocOSU (N-(9-Fluorenylmethoxycarbonyloxy)-succinimid) (148.5 g, 440 mmol) solved in dioxan (2.00 l) was added. Then saturated sodium hydrogencarbonate solution (800 ml, 880 mmol) was added slowly. The mixture was stirred 3 h at room temperature until TLC (Silicagel Merck 60, chloroform/methanol/acetic acid 8:2+0.1% v/v/v) showed complete consumption of the educts. The obtained precipitate was filtered off and the filtrate was added to water (6.00 l). The resulting suspension was stirred for 5 min and then stored 12 h at 4° C. The resulting suspension was filtered. The obtained solid was washed with cold water (3.00 l) and dried 12 h under reduced pressure at 45° C. over calcium chloride. For a further purification the crude product was suspended in ethylacetate, stirred 1 h, filtered and dried under reduced pressure yielding 134 g (95%) of the title compound as white solid.

Workup

  1. additionwas added
  2. customconsumption of the educts
  3. filtrationThe obtained precipitate was filtered off
  4. additionthe filtrate was added to water (6.00 l)
  5. waitstored 12 h at 4° C
  6. filtrationThe resulting suspension was filtered
  7. washThe obtained solid was washed with cold water (3.00 l)
  8. dry with materialdried 12 h under reduced pressure at 45° C. over calcium chloride
  9. customFor a further purification the crude product
  10. stirringstirred 1 h
  11. filtrationfiltered
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-e314e1c8b88c40a981c72daf8067e749
Source dataset
uspto-grants-2014_06
Patent number
US08754111B2

Reaction notes

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