1,1,1,3,3,3-Hexafluoro-2-propanol → HCID 89677405, compound

HRID 2278286Notes

Reaction equation

HRID 2278286 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[F:13][C:14]([F:22])([F:21])[CH:15]([OH:20])[C:16]([F:19])([F:18])[F:17].C(N(CC)C(C)C)(C)C.[CH3:32][C:33]1[N:38]=[C:37]([CH2:39][N:40]2[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]2)[CH:36]=[CH:35][C:34]=1[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1[CH3:52]>ClCCl>[CH3:32][C:33]1[N:38]=[C:37]([CH2:39][N:40]2[CH2:41][CH2:42][N:43]([C:5]([O:20][CH:15]([C:16]([F:19])([F:18])[F:17])[C:14]([F:22])([F:21])[F:13])=[O:11])[CH2:44][CH2:45]2)[CH:36]=[CH:35][C:34]=1[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1[CH3:52]

Participants

6

Reactant 4

HCID 135291,1,1,3,3,3-Hexafluoro-2-propanolHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 89676844HCID 89676844, compound

Product 1

HCID 89677405HCID 89677405, compoundYield 164.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 40 mL vial was charged with a solution of triphosgene (83.0 mg, 0.280 mmol, 0.39 equiv) in dichloromethane (20 mL), 1,1,1,3,3,3-hexafluoropropan-2-ol (141 mg, 0.840 mmol, 1.18 equiv). N,N-Diisopropylethylamine (542 mg, 4.19 mmol, 5.90 equiv) was added dropwise at 0° C. The mixture was stirred for 2 hours at room temperature. 1-[[6-Methyl-5-(2-methylphenyl)pyridin-2-yl]methyl]piperazine (200 mg, 0.710 mmol, 1.00 equiv) was added. The resulting solution was stirred overnight at room temperature and concentrated under reduced pressure. The residue was chromatographed on a C18 column with acetonitrile/water (40/60) to provide 219 mg (65% yield) of 1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[6-methyl-5-(2-methylphenyl)pyridin-2-yl]methyl]piperazine-1-carboxylate as yellow oil. 1H NMR 300 MHz (CDCl3) δ 7.43 (d, J=7.5 Hz, 1H), 7.28-7.34 (m, 4H), 7.09 (d, J=6.9 Hz, 1H), 5.72-5.80 (m, 1H), 3.77 (s, 2H), 3.65 (br, 4H), 2.63 (br, 4H), 2.31 (s, 3H), 2.07 (s, 3H). LCMS (ESI, m/z): 476 [M+H]+.

Workup

  1. stirringThe resulting solution was stirred overnight at room temperature
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was chromatographed on a C18 column with acetonitrile/water (40/60)

Sources & evidence

ORD record
ord-e531bd11459b4e90b056627fc0a8744e
Source dataset
uspto-grants-2015_09
Patent number
US09133148B2

Reaction notes

Loading…