(3aS)-1-methyl-3,3-diphenyl-hexahydropyrrolo(1,2-c)(1,3,2)oxazaborole → (R)-tert-butyl 4-((5-hydroxyhexyl)oxy)-4-methylpiperidine-1-carboxylate

HRID 921143Notes

Reaction equation

HRID 921143 reaction equation
[CH3:1][C:2]1([O:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20](=[O:22])[CH3:21])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.CB1N2CCC[C@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])([O-])=O.[Na+].[Na+]>[OH:22][C@H:20]([CH3:21])[CH2:19][CH2:18][CH2:17][CH2:16][O:15][C:2]1([CH3:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1

Participants

6

Reactant 2

HCID 2734713(3aS)-1-methyl-3,3-diphenyl-hexahydropyrrolo(1,2-c)(1,3,2)oxazaboroleHCID 118307169Tert-butyl 4-methyl-4-((5-oxohexyl)oxy)piperidine-1-carboxylate

Product 1

HCID 118307135(R)-tert-butyl 4-((5-hydroxyhexyl)oxy)-4-methylpiperidine-1-carboxylateYield 79%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
-35 °C

Procedure

To a stirred yellow solution of tert-butyl 4-methyl-4-((5-oxohexyl)oxy)piperidine-1-carboxylate (5.8 g, 18.50 mmol) in anhydrous toluene (100 mL) was added (S)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (2.052 g, 7.40 mmol). The mixture was cooled to −35° C. and a solution of 50% catechoborane (6.35 mL, 25.9 mmol) in toluene was added over 5 min. After 30 min, the reaction mixture was slowly warmed to −15° C. and stirred for additional 2 h. At his point LCMS indicated completion of reaction. Mixture was then diluted with EtOAc (200 mL) and sat. Na2CO3 (100 mL). The mixture was stirred vigorously for 30 min, and the organic phase washed with sat Na2CO3 (2×50 mL), dried (Na2SO4), filtered, concentrated and the residue was purified by silica gel chromatography (5-70% EtOAc/hexane) to afford desired (R)-tert-butyl 4-((5-hydroxyhexyl)oxy)-4-methylpiperidine-1-carboxylate (4.6 g, 14.58 mmol, 79% yield) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 3.90-3.80 (m, 1H), 3.78-3.64 (m, 2H), 3.33 (t, J=6.4 Hz, 2H), 3.14 (t, J=11.4 Hz, 2H), 1.74 (d, J=13.2 Hz, 2H), 1.66-1.54 (m, 3H), 1.53-1.46 (m, 12H), 1.46-1.38 (m, 3H), 1.22 (d, J=6.3 Hz, 3H), 1.17 (s, 3H). LCMS (M+Na)=338.4.

Workup

  1. temperaturethe reaction mixture was slowly warmed to −15° C.
  2. customcompletion of reaction
  3. stirringThe mixture was stirred vigorously for 30 min
  4. washthe organic phase washed
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue was purified by silica gel chromatography (5-70% EtOAc/hexane)

Sources & evidence

ORD record
ord-9967290609914ef394a9029730276a0b
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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