Diisopropylethylamine → (R)-tert-Butyl 2,2,4-trimethyl-4-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl)thiazol-2-yl)oxazolidine-3-carboxylate

HRID 2357091Notes

Reaction equation

HRID 2357091 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@:12]([CH3:16])([C:13](O)=O)[CH2:11][O:10][C:9]1([CH3:18])[CH3:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl.[NH2:53][CH2:54][C:55]([C:57]1[CH:62]=[CH:61][C:60]([O:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH3:71])=[C:59]([C:72]([F:75])([F:74])[F:73])[CH:58]=1)=O.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:85])=CC=1>C(Cl)Cl.C1(C)C=CC=CC=1>[CH3:17][C:9]1([CH3:18])[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C@@:12]([CH3:16])([C:13]2[S:85][C:55]([C:57]3[CH:62]=[CH:61][C:60]([O:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH3:71])=[C:59]([C:72]([F:75])([F:74])[F:73])[CH:58]=3)=[CH:54][N:53]=2)[CH2:11][O:10]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 87949Lawesson's reagentHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 52987736HCID 52987736, compoundHCID 684532372-Amino-1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone hydrochloride

Product 1

HCID 59384295(R)-tert-Butyl 2,2,4-trimethyl-4-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl)thiazol-2-yl)oxazolidine-3-carboxylateYield 41%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-3-(tert-Butoxycarbonyl)-2,2,4-trimethyloxazolidine-4-carboxylic acid (D3) (100 mg, 1 equiv), HATU (220 mg, 1.5 equiv), and DIEA (0.67 mL, 10 equiv) in DCM (5 mL) was added 2-amino-1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone hydrochloride (D2) (142 mg, 1.0 equivalents). The solvent removed in vacuo and the product was purified with silica gel column chromatography using the Combi-Flash system (Hex:EtOAc). This resulted in a colourless, thick oil which was dissolved in toluene (5 mL) with Lawesson's reagent (280 mg, 3 equiv). The resultant mixture was heated at 120° C. for 2 hours to produce the title product as a colourless oil 41% yield (90 mg). TLC (1:2 EtOAc:Hex), Rf=0.3; MS (ESI, M+Na)=572.99; 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 8.11 (d, 1H, J=8.4 Hz), 7.05 (d, 1H, J=8.4 Hz), 4.62-4.79 (m, 2H), 4.13 (t, 2H, J=6.4 Hz), 3.28 (br s, 1H), 1.22-1.90 (m, 30H), 0.89 (t, 3H, J=6.4 Hz).

Workup

  1. customThe solvent removed in vacuo
  2. customthe product was purified with silica gel column chromatography
  3. customThis resulted in a colourless, thick oil which

Sources & evidence

ORD record
ord-868fcabb46524d1b878aba3885d6f724
Source dataset
uspto-grants-2010_07
Patent number
US07759370B2

Reaction notes

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