Ethanol → 1,1-dimethylethyl (3S)-3-(2-hydrazino-2-oxoethyl)-1-pyrrolidinecarboxylate

HRID 525154Notes

Reaction equation

HRID 525154 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([CH2:13][C:14]([OH:16])=O)[CH2:9]1)=[O:7])([CH3:4])[CH3:3].C(O)C.O.[NH2:21][NH2:22]>C(OCC)C.CN(C)C1C=CN=CC=1>[NH:21]([C:14](=[O:16])[CH2:13][C@@H:10]1[CH2:11][CH2:12][N:8]([C:6]([O:5][C:2]([CH3:4])([CH3:3])[CH3:1])=[O:7])[CH2:9]1)[NH2:22]

Participants

6

Reactant 3

HCID 702EthanolHCID 24654Hydrazine hydrate (1:1)HCID 1502098(S)-2-(1-(tert-butoxycarbonyl)pyrrolidin-3-yl)acetic acid

Product 1

HCID 866748261,1-dimethylethyl (3S)-3-(2-hydrazino-2-oxoethyl)-1-pyrrolidinecarboxylateYield 88%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolvent2×

Procedure

A solution of ((3S)-1-{[(1,1-dimethylethyl)oxy]carbonyl}-3-pyrrolidinyl)acetic acid (5 g, 21.81 mmol) in diethyl ether (50 mL) was treated with N,N-dimethyl-4-pyridinamine (2.181 mmol), N-[3-(dimethylamino)propyl]-N-ethylcarbodiimide(HCl) (23.99 mmol), and ethanol (48.0 mmol) and was stirred at room temperature overnight. Analysis by LCMS indicated that all starting material had converted to the desired methyl ester. The reaction contents were diluted with ether (100 mL) and washed with saturated aq NaHSO4 solution, water, and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. The resulting clear oil was dissolved in ethanol (25 mL), treated with hydrazine monohydrate (436 mmol), and was stirred overnight at 80° C. LCMS analysis indicated complete conversion of the intermediate. The reaction solution was concentrated to dryness in vacuo to afford the title compound as a clear oil (4.65 grams, 88% yield). No further purification was utilized. MS(ES)+ m/e 244.2 [M+H]+.

Workup

  1. customThe reaction contents
  2. washwashed with saturated aq NaHSO4 solution, water, and brine
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness in vacuo
  6. dissolutionThe resulting clear oil was dissolved in ethanol (25 mL)
  7. stirringwas stirred overnight at 80° C
  8. concentrationThe reaction solution was concentrated to dryness in vacuo

Sources & evidence

ORD record
ord-5d91d577350244f58aa16de36dfcd507
Source dataset
uspto-grants-2016_05
Patent number
US09340529B2

Reaction notes

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