Nitrogen → (2S,4R)-1-tert-butyl 2-methyl 4-(aminooxy)pyrrolidine-1,2-dicarboxylate

HRID 656590Notes

Reaction equation

HRID 656590 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1.O[N:19]1C(=O)C2C(=CC=CC=2)C1=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.N#N.O.NN>C(Cl)Cl>[NH2:19][O:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1

Participants

8

Reactant 6

HCID 947NitrogenHCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 24654Hydrazine hydrate (1:1)HCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 57999148(2S,4R)-1-tert-butyl 2-methyl 4-(aminooxy)pyrrolidine-1,2-dicarboxylateYield 53.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (4.9 g, 20.0 mmol) in CH2Cl2 (50.0 mL) was added 2-hydroxyisoindolin-1,3-dione (3.26 g, 20.0 mmol) and triphenylphosphine (7.86 g, 30.0 mmol). The resultant mixture was cooled to 0° C. and diisopropylazodicarboxylate (5.90 ml, 30.0 mmol) was slowly added drop wise under N2 atmosphere. The reaction mixture was stirred at ambient temperature for 48 h. Work-up and purification as described in Example 2A, Step 1 afforded (2S,4R)-1-tert-butyl 2-methyl 4-(1,3-dioxoisoindolin-2-yloxy)pyrrolidine-1,2-dicarboxylate as a viscous oil. The resultant oily compound was dissolved in CH2Cl2 (100 ml) and cooled to 0° C. Hydrazine hydrate (4.0 mL, 40.0 mmol) was added drop wise. The reaction mixture was stirred at ambient temperature over night. Work-up and purification as described in Example 2A, Step 2 afforded (2.8 g, 53%, over two steps) of (2S,4R)-1-tert-butyl 2-methyl 4-(aminooxy)pyrrolidine-1,2-dicarboxylate as a pale yellow oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.42 (s, 9H) 2.13-2.29 (m, 1H) 2.34-2.48 (m, 1H) 3.48-3.68 (m, 2H) 3.72 (s, 3H) 4.23-4.30 (m, 1H) 4.30-4.49 (m, 1H). MS (ES) [M+H] calculated for C11H21N2O5, 261.14. found 261.22.

Workup

  1. custompurification
  2. dissolutionThe resultant oily compound was dissolved in CH2Cl2 (100 ml)
  3. temperaturecooled to 0° C
  4. stirringThe reaction mixture was stirred at ambient temperature over night
  5. custompurification

Sources & evidence

ORD record
ord-e92c8d9b90554be89beab32e86ebc076
Source dataset
uspto-grants-2011_12
Patent number
US08071766B2

Reaction notes

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