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

HRID 2357060Notes

Reaction equation

HRID 2357060 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@:12]([CH3:16])([C:13]([OH:15])=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:56]>CCOC(C)=O.CN(C=O)C>[CH3:17][C:9]1([CH3:18])[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@@:12]([CH3:16])([C:13](=[O:15])[NH:53][CH2:54][C:55]([C:57]2[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:73])([F:74])[F:75])[CH:58]=2)=[O:56])[CH2:11][O:10]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 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 59384447(R)-tert-Butyl 2,2,4-trimethyl-4-(2-(4-(octyloxy)-3-(trifluoromethyl)phenyl)-2-oxoethylcarbamoyl)oxazolidine-3-carboxylateYield 40%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

To a solution of protected oxazolidine-4-carboxylic acid 4 (176 mg, 1 equivalents), HATU (310 mg, 1.2 equivalents), and DIEA (1.2 mL, 10 equivalents) in CH2CL2/DMF (1:1, 10 mL) was added amino-acetophenone 3 (250 mg, 1.0 equivalents). The resultant mixture was stirred at room temperature overnight. The reaction mixture was diluted with EtOAc (50 mL) and washed with 10% NH4Cl (2×50 mL) and saturated NaCl (1×50 mL). The solvent removed in vacuo and the product was obtained, silica gel column chromatography using the Combi-Flash system (Hex:EtOAc), as a white solid in 40% yield (185 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. washwashed with 10% NH4Cl (2×50 mL) and saturated NaCl (1×50 mL)
  2. customThe solvent removed in vacuo
  3. customthe product was obtained

Sources & evidence

ORD record
ord-33292b19ae8e466db178854d5d9f316c
Source dataset
uspto-grants-2010_07
Patent number
US07759370B2

Reaction notes

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