2,2,2-Trifluoroethanol → Tert-butyl 4-[(2,2,2-trifluoroethoxy)methyl]piperidine-1-carboxylate

HRID 341512Notes

Reaction equation

HRID 341512 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.[F:16][C:17]([F:21])([F:20])[CH2:18]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OC(C)(C)C)=O)=O)(C)(C)C>C1COCC1>[F:16][C:17]([F:21])([F:20])[CH2:18][O:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 66802837Tert-butyl 4-[(2,2,2-trifluoroethoxy)methyl]piperidine-1-carboxylateYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl 4-(hydroxymethyl)piperidine-1-carboxylate (0.300 g, 1.393 mmol), 2,2,2-trifluoroethan-1-ol (1.00 mL, 13.935 mmol), triphenylphosphine (0.440 g, 1.672 mmol) and N-{[(tert-butoxy)carbonyl]imino}(tert-butoxy)formamide (0.390 g, 1.672 mmol) were combined in THF (10 mL) and stirred at room temperature for 36 h before being heated to 75 C for 18 h. The reaction mixture was concentrated under reduced pressure and purified by FCC (EtOAc: heptane, 1:1) to afford the title compound (0.192 g, 50%). Method B HPLC-MS: MH+ requires m/z=297 Found: m/z=242 (MH+-tBu), Rt=2.25 min (100%).

Workup

  1. temperaturebefore being heated to 75 C for 18 h
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. custompurified by FCC (EtOAc: heptane, 1:1)

Sources & evidence

ORD record
ord-d102fc70078f44939f552f8f76702499
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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