N,N,N',N'-Tetramethylethylenediamine → tert-Butyl 2-(1-((benzyloxy)carbonyl)-3-hydroxyazetidin-3-yl)piperidine-1-carboxylate

HRID 605677Notes

Reaction equation

HRID 605677 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C)CCN(C)C.CC(C)C[Li].[O:27]=[C:28]1[CH2:31][N:30]([C:32]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:33])[CH2:29]1>C(OCC)C>[OH:27][C:28]1([CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][N:1]2[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:29][N:30]([C:32]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:33])[CH2:31]1

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 7010304N-(tert-butoxycarbonyl)piperidineHCID 10632047Benzyl 3-oxoazetidine-1-carboxylateHCID 178506859HCID 178506859, compound

Product 1

HCID 59469243tert-Butyl 2-(1-((benzyloxy)carbonyl)-3-hydroxyazetidin-3-yl)piperidine-1-carboxylateYield 13%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 1,1-dimethylethyl piperidine-1-carboxylate (0.50 g, 2.7 mmol) in anhydrous diethyl ether (9.0 mL) under anhydrous nitrogen gas was added N,N,N′,N′-tetramethylethane-1,2-diamine (0.41 mL, 2.7 mmol), and the solution was cooled to −78° C. To this solution was added (2-methylpropyl)lithium (2.1 mL, 1.4 M in cyclohexane, 3.0 mmol) in small portions. To this anion solution was added phenylmethyl 3-oxoazetidine-1-carboxylate (1.0 g, 5.4 mmol), prepared using procedures as described in Reference 3, in anhydrous ether (2.0 mL), while maintaining the internal temperature at less than −60° C. The solution was allowed to warm to room temperature and stirred overnight. The reaction was quenched with water, and partitioned between water and diethyl ether. The layers were separated and the aqueous layer was extracted with diethyl ether twice. The combined organic layers were dried (magnesium sulfate), filtered and concentrated in vacuo. Chromatography (silica gel, 3:1 hexanes/ethyl acetate) gave 0.13 g (13%) of 1,1-dimethylethyl 2-(3-hydroxy-1-{[(phenylmethyl)oxy]carbonyl}azetidin-3-yl)piperidine-1-carboxylate. 1H NMR (400 MHz, CDCl3): 7.31 (m, 5H), 5.08 (s, 2H), 4.05 (d, 1H), 4.00 (d, 1H), 3.84 (d, 2H), 3.80 (broad s, 1H), 3.55 (broad s, 1H), 3.10 (broad s, 1H), 1.92 (m, 1H), 1.45-1.62 (m, 6H), 1.43 (s, 9H). MS (EI) for C21H30N2O5: 335 (M-tBu), 315 (M-OtBu).

Workup

  1. customprepared
  2. temperaturewhile maintaining the internal temperature at less than −60° C
  3. temperatureto warm to room temperature
  4. customThe reaction was quenched with water
  5. custompartitioned between water and diethyl ether
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with diethyl ether twice
  8. dry with materialThe combined organic layers were dried (magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8bfc748742cb42feba7981be46bc677e
Source dataset
uspto-grants-2011_03
Patent number
US07915250B2

Reaction notes

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