Water → 1-[(tert-butoxy)carbonyl]-3-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)azetidine-3-carboxylic acid

HRID 1772366Notes

Reaction equation

HRID 1772366 reaction equation
[NH2:1][C:2]1([C:13]([OH:15])=[O:14])[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.C(=O)([O-])[O-].[Na+].[Na+].O.[C:23](Cl)(=[O:39])[O:24][CH2:25][CH:26]1[C:38]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[C:32]2[C:27]1=[CH:28][CH:29]=[CH:30][CH:31]=2>O1CCOCC1>[CH:37]1[C:38]2[CH:26]([CH2:25][O:24][C:23]([NH:1][C:2]3([C:13]([OH:15])=[O:14])[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:10])[CH3:11])=[O:7])[CH2:3]3)=[O:39])[C:27]3[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:33]=2[CH:34]=[CH:35][CH:36]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 343679-Fluorenylmethyl chloroformateHCID 534147103-Amino-1-[(tert-butoxy)carbonyl]azetidine-3-carboxylic acid

Product 1

HCID 678143551-[(tert-butoxy)carbonyl]-3-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)azetidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A round bottomed flask was charged with 3-amino-1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (prepared according the procedure described in Synthesis 1991, 783-784.) (2.464 mmol), sodium carbonate (1.3 g, 12.32 mmol), a stir bar and water (70 mL). (9H-fluoren-9-yl)methyl carbonochloridate (1.9 g, 7.39 mmol) in 1,4-dioxane (50 mL) was added and the milky solution was stirred overnight at rt. The next day the reaction was poured into a separatory funnel and the aqueous solution washed with diethyl ether (repeated twice) (organic phases were discarded at this stage). The aqueous phase was acidified to pH 2-3 with 1 M HCl (a precipitate was formed) and the product was extracted with EtOAc (repeated 3 times). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The solid was used without purification in the next step. LRMS (M+Na)+: 461 m/z.

Workup

  1. customprepared
  2. customdescribed in Synthesis 1991, 783-784
  3. additionThe next day the reaction was poured into a separatory funnel
  4. washthe aqueous solution washed with diethyl ether (
  5. customwas formed) and the product
  6. extractionwas extracted with EtOAc (repeated 3 times)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customThe solid was used without purification in the next step

Sources & evidence

ORD record
ord-1f0d26d086ab40e9991acb1bd10f315e
Source dataset
uspto-grants-2016_02
Patent number
US09249161B2

Reaction notes

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