Di-tert-butyl dicarbonate → 3,6-Diaza-bicyclo(3.2.0)heptane-6-carboxylic acid tert-butyl ester

HRID 1193073Notes

Reaction equation

HRID 1193073 reaction equation
C(OC([N:11]1[CH2:15][CH:14]([CH2:16]O)[CH:13]([NH:18][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:12]1)=O)C1C=CC=CC=1.C(OC(N1CC(CO)C(N)C1)=O)C1C=CC=CC=1.C(=O)(O)[O-].[Na+].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>C(O)CCCC.C(O)C.O>[C:22]([O:21][C:19]([N:18]1[CH2:16][CH:14]2[CH:13]1[CH2:12][NH:11][CH2:15]2)=[O:20])([CH3:25])([CH3:24])[CH3:23]

Participants

7

Reactant 4

HCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 18465917Phenylmethyl 3-amino-4-(hydroxymethyl)-1-pyrrolidinecarboxylateHCID 18465918HCID 18465918, compound

Product 1

HCID 467381813,6-Diaza-bicyclo(3.2.0)heptane-6-carboxylic acid tert-butyl esterYield 64%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21272853HCID 21272853, compoundSolvent

Procedure

3-tert-Butoxycarbonylamino-4-hydroxymethyl-pyrrolidine-1-carboxylic acid benzyl ester. To a 3 L round-bottomed flask, was added the filtered reaction mixture of 3-amino-4-hydroxymethyl-pyrrolidine-1-carboxylic acid benzyl ester in pentanol/ethanol mixture. To the mixture sodium bicarbonate (30.8 g, 367 mmol), H2O (655 mL), and Boc anhydride (38 g, 174.1 mmol) were added. The mixture was stirred under N2(g) for 15 h at room temperature. The biphasic mixture was then separated and the organics were washed with brine (655 mL). The organics were dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The material was warmed to 98° C. in toluene/heptanes (280 mL each) and then filtered. The filtrate was slowly cooled to room temperature and stirred for 20 h. The resulting solids were filtered and washed with heptanes to provide the title compound (39.5 g, 64% over two steps). 1H-NMR (CD3OD, 400 MHz): 7.31 (m, 5H), 5.11 (s, 2H), 4.20 (m, 1H), 3.50-3.70 (m, 4H), 3.34-3.42 (m, 1H), 3.18-3.29 (m, 1H), 2.49 (m, 1H), 1.44 (s, 9H).

Workup

  1. additionTo a 3 L round-bottomed flask, was added
  2. customThe biphasic mixture was then separated
  3. washthe organics were washed with brine (655 mL)
  4. dry with materialThe organics were dried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. temperatureThe material was warmed to 98° C. in toluene/heptanes (280 mL each)
  8. filtrationfiltered
  9. temperatureThe filtrate was slowly cooled to room temperature
  10. stirringstirred for 20 h
  11. filtrationThe resulting solids were filtered
  12. washwashed with heptanes

Sources & evidence

ORD record
ord-03d47f2b2a134de8ae8993aaf3162fc6
Source dataset
uspto-grants-2014_03
Patent number
US08680275B2

Reaction notes

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