Triphenylphosphine → tert-Butyl 4-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)piperidine-1-carboxylate

HRID 2409542Notes

Reaction equation

HRID 2409542 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([B:9]2[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]2)[CH:6]=[CH:5][C:4]=1[OH:18].[C:19]([N:26]1[CH2:31][CH2:30][CH:29](O)[CH2:28][CH2:27]1)([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].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>C1COCC1.CCOC(C)=O>[C:22]([O:21][C:19]([N:26]1[CH2:31][CH2:30][CH:29]([O:18][C:4]2[CH:5]=[CH:6][C:7]([B:9]3[O:10][C:11]([CH3:17])([CH3:16])[C:12]([CH3:14])([CH3:15])[O:13]3)=[CH:8][C:3]=2[O:2][CH3:1])[CH2:28][CH2:27]1)=[O:20])([CH3:25])([CH3:23])[CH3:24]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 27346502-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 53217119tert-Butyl 4-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)piperidine-1-carboxylateYield 71.5%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (0.8 g, 3.2 mmol, 1 eq), 1-boc-4-hydroxypiperidine (0.97 g, 4.8 mmol, 1.5 eq) and triphenylphosphine (1.26 g, 4.8 mmol, 1.5 eq) in anhydrous THF (8 mL) was added DIAD (0.94 mL, 4.8 mmol, 1.5 eq) dropwise at 0° C. The solution was stirred at RT for 45 h. The solvent was removed, and the resulting light orange oily residue was treated with 20% AcOEt/c-hexane to give white crystals (PPh3O) which were filtered off and washed with the same mixture. The filtrate was evaporated to give an oily residue which was treated with c-hexane and a few drops of AcOEt to give a white precipitate that was removed by filtration and an oily residue that solidified upon standing. The crude product (1.93 g containing some c-hexane) was used as it was in the subsequent step. The remainder was purified by column chromatography (Isolute Flash Si II column, 25 g silica gel, 0-8% AcOEt in c-hexane) to give the pure desired product (0.991 g). HPLC-MS (10-95% B in 4 min at 0.5 mL+2 min 100% B, flow 0.8 mL/min, 50° C.): tR=5.10 min, [M+H]+ m/z 334.3.

Workup

  1. customThe solvent was removed
  2. additionthe resulting light orange oily residue was treated with 20% AcOEt/c-hexane
  3. customto give white crystals (PPh3O) which
  4. filtrationwere filtered off
  5. washwashed with the same mixture
  6. customThe filtrate was evaporated
  7. customto give an oily residue which
  8. customto give a white precipitate that
  9. customwas removed by filtration
  10. additionThe crude product (1.93 g containing some c-hexane)
  11. customThe remainder was purified by column chromatography (Isolute Flash Si II column, 25 g silica gel, 0-8% AcOEt in c-hexane)

Sources & evidence

ORD record
ord-d036b41c8daa47428bbe7c9494a0d0ce
Source dataset
uspto-grants-2014_08
Patent number
US08815918B2

Reaction notes

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