Hydrochloric Acid → (8S)-di-tert-butyl 2-oxo-1-oxa-3,7-diazaspiro[4.4]nonane-7,8-dicarboxylate

HRID 2038554Notes

Reaction equation

HRID 2038554 reaction equation
C(OC(=O)[CH2:5][C:6]1([OH:25])[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@H:8]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:7]1)C.NN.Cl.[N:30]([O-])=O.[Na+].[CH3:34][OH:35]>C(Cl)(Cl)Cl.C1C=CC=CC=1>[O:35]=[C:34]1[NH:30][CH2:5][C:6]2([CH2:7][C@@H:8]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10]2)[O:25]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 9321HydrazineHCID 23668193Sodium NitriteHCID 59547296(2S)-di-tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypyrrolidine-1,2-dicarboxylate

Product 1

HCID 59547287(8S)-di-tert-butyl 2-oxo-1-oxa-3,7-diazaspiro[4.4]nonane-7,8-dicarboxylate

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6212ChloroformSolvent

Procedure

(2S)-di-tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypyrrolidine-1,2-dicarboxylate (A1) (1.58 g, 4.42 mmol, 1 eq.) was diluted in methanol (6 mL). To this mixture, hydrazine (0.417 mL, 13.26 mmol, 3 eq.) was added. The reaction was stirred at room temp. overnight then concentrated. To the residue, 0.5 N HCl (22.1 mL, 11.05 mmol, 2.5 eq.) was added and the mixture was sonnicated until the residue dissolved in the acid. The solution was cooled in an icewater bath. A 1.0 M solution of NaNO2 (5.3 mL, 5.3 mmol, 1.2 eq.) was added slowly and stirred for 15 min. A 1:1 benzene:chloroform mixture was added, the organic layer was separated and added slowly to refluxing benzene (2×). The reaction was refluxed for 1 hr then concentrated. Chromatography using DCM and 20% MeOH in DCM gave 0.978 g (2.86 mmol) of (8S)-di-tert-butyl 2-oxo-1-oxa-3,7-diazaspiro[4.4]nonane-7,8-dicarboxylate (B1) as a 4:1 (5S,8S:5S,8R) mixture of the diastereomers. 1H NMR (300 MHz, DMSO) 7.63 (m, 1H), 4.29-4.09 (m, 1H), 3.65-3.39 (m, 4H), 2.5-2.0 (m, 2H), 1.43-1.18 (m, 18H).

Workup

  1. concentrationthen concentrated
  2. dissolutiondissolved in the acid
  3. temperatureThe solution was cooled in an icewater bath
  4. stirringstirred for 15 min
  5. customthe organic layer was separated
  6. additionadded slowly
  7. temperatureto refluxing benzene (2×)
  8. temperatureThe reaction was refluxed for 1 hr
  9. concentrationthen concentrated

Sources & evidence

ORD record
ord-42c940f08f8f4a488ad6ec5bf24eb94d
Source dataset
uspto-grants-2013_11
Patent number
US08575208B2

Reaction notes

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