2,2,2-Trifluoroethanol → HCID 59806009, compound

HRID 1661501Notes

Reaction equation

HRID 1661501 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:19]=[CH:18][C:10]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][CH:8]=2)[CH2:3]1.CCN(CC)CC.Cl[C:28](Cl)([O:30][C:31](=[O:37])OC(Cl)(Cl)Cl)Cl.[F:39][C:40]([F:44])([F:43])CO>ClCCl>[F:39][C:40]([F:44])([F:43])[CH2:28][O:30][C:31]([NH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:19]=[CH:18][C:10]([C:11]([O:13][C:14]([CH3:16])([CH3:15])[CH3:17])=[O:12])=[CH:9][CH:8]=2)[CH2:3]1)=[O:37]

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 8471TriethylamineHCID 94429TriphosgeneHCID 58930644HCID 58930644, compound

Product 1

HCID 59806009HCID 59806009, compoundYield 158.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

The compound 17 (400 mg, 1.52 mmol) and Et3N (850 ml, 6.10 mmol) were added to a stirring solution of triphosgene (181 mg, 0.61 mmol) in dichloromethane (8 mL) at −60° C. The reaction mixture was allowed to warm to room temperature and stirred for additional 2 h. 2,2,2-Trifluoroethanol (133 μl, 1.82 mmol) was added and the reaction mixture was stirred for 16 h, diluted with dichloromethane, washed with saturated aqueous NH4Cl, NaHCO3 and brine, dried over MgSO4, filtered and concentrated in vacuo. The solid residue was purified by flash chromatography (eluent 0.5-1% MeOH-dichloromethane) to afford the title compound 139 as a white solid (375 mg, 64% yield). 1H NMR: (DMSO) δ(ppm): 8.09 (d, J=6.8 Hz, 1H), 7.70 (d, J=8.8 Hz, 2H), 6.52 (d, J=8.8, 2H), 4.66 (q, J=9.1 Hz, 2H), 4.24-4.20 (m, 1H), 3.57-3.53 (m, 1H), 3.47-3.41 (m, 1H), 3.36-3.30 (m, 1H, overlap with water), 3.19-3.16 (m, 1H), 2.21-2.16 (m, 1H), 1.99-1.93 (m, 1H), 1.50 (s, 9H). LRMS (ESI): (calc.) 388.2; (obt.) 389.2 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred for 16 h
  2. washwashed with saturated aqueous NH4Cl, NaHCO3 and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe solid residue was purified by flash chromatography (eluent 0.5-1% MeOH-dichloromethane)

Sources & evidence

ORD record
ord-7eb138d06d6b4c5095bc1b1985e6b015
Source dataset
uspto-grants-2011_10
Patent number
US08030344B2

Reaction notes

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