Triphenylphosphine → HCID 15895217, compound

HRID 1384976Notes

Reaction equation

HRID 1384976 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][C@H:22]([CH2:26][OH:27])[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[Br:28][C:29]1[CH:34]=[C:33]([CH3:35])[C:32](O)=[C:31]([CH3:37])[CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.CCOCC.CCCCCC>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH2:23][C@H:22]([CH2:26][O:27][C:32]2[C:33]([CH3:35])=[CH:34][C:29]([Br:28])=[CH:30][C:31]=2[CH3:37])[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 169194-Bromo-2,6-dimethylphenolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1514448tert-Butyl (3S)-3-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 15895217HCID 15895217, compoundYield 118.9%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A solution of diethyl azodicarboxylate (16.1 mL, 102.2 mmol) in tetrahydrofuran (50 mL) was added dropwise during 1.5 hours to an ice cold solution of (S)-N-(tert-butoxycarbonyl)-3-hydroxymethylpiperidine (20.0 g, 92.9 mmol), 4-bromo-2,6 dimethylphenol (18.7 g, 92.9 mmol), and triphenylphosphine (26.8 g, 102.2 mmol) in tetrahydrofuran (300 mL), while maintaining the temperature below 10° C. After the addition was complete, the reaction was stirred at room temperature for 48 hours and partitioned between ethyl acetate (1L) and water (1L). After extracting the aqueous phase with additional ethyl acetate (2×200 mL), the combined ethyl acetate layers were washed with brine (250 mL), dried over magnesium sulfate, and concentrated to afford a thick yellow oil. The oil was combined with hexane (500 mL) and ether (50 mL) and stirred for 30 minutes. The resulting white precipitate was removed by filtration and washed with additional hexane (50 mL). The combined filtrates were concentrated to give crude (S)-N-(tert-butoxycarbonyl)-3-(4-bromo-2,6-dimethylphenoxymethyl) piperidine as a clear yellow oil (44 g).

Workup

  1. temperaturewhile maintaining the temperature below 10° C
  2. additionAfter the addition
  3. custompartitioned between ethyl acetate (1L) and water (1L)
  4. extractionAfter extracting the aqueous phase with additional ethyl acetate (2×200 mL)
  5. washthe combined ethyl acetate layers were washed with brine (250 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customto afford a thick yellow oil
  9. stirringstirred for 30 minutes
  10. customThe resulting white precipitate was removed by filtration
  11. washwashed with additional hexane (50 mL)
  12. concentrationThe combined filtrates were concentrated

Sources & evidence

ORD record
ord-74587cbd213f4953aa3e0045ce402efb
Source dataset
uspto-grants-2001_07
Patent number
US06262078B1

Reaction notes

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