Diisopropylethylamine → HCID 58488008, compound

HRID 888228Notes

Reaction equation

HRID 888228 reaction equation
[CH3:1][C:2]1([CH3:16])[O:6][C@H:5]([C@H:7]([CH2:11][CH:12]([CH3:14])[CH3:13])[C:8]([OH:10])=O)[C:4](=[O:15])[O:3]1.C(OC(C)C)(=O)[C@@H](CC(OC(C)C)=O)O.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.FC(N(C)C)=[N+](C)C.[CH3:56][O:57][C:58]1[CH:63]=[CH:62][C:61]([N:64]2[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]2)=[CH:60][CH:59]=1>C(Cl)Cl>[CH3:56][O:57][C:58]1[CH:59]=[CH:60][C:61]([N:64]2[CH2:69][CH2:68][N:67]([C:8]([C@H:7]([C@H:5]3[O:6][C:2]([CH3:1])([CH3:16])[O:3][C:4]3=[O:15])[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:10])[CH2:66][CH2:65]2)=[CH:62][CH:63]=1

Participants

7

Reactant 5

HCID 81531Diisopropylethylamine2×HCID 2697221-(4-Methoxyphenyl)piperazineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 10921962Diisopropyl (R)-(+)-malateHCID 22876674HCID 22876674, compound

Product 1

HCID 58488008HCID 58488008, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a cold solution (0° C.) of (2S)-2-[(4R)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoic acid (prepared according to WO 94/02447 or similarly to Seebach et al., 1990, Org. Syntheses, Coll. Vol. III, p 153-159 but starting from diisopropyl (R)-(+)-malate, 150 mg, 0.65 mmol) in anhydrous DCM (3 mL) were added DIEA (115 μL, 0.69 mmol) and fluoro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (190 mg, 0.72 mmol, Aldrich). The reaction mixture was stirred at 0° C. for 40 min. Then a solution of 1-(4-methoxyphenyl)-piperazine (138 mg, 0.72 mmol, Chess) and DIEA (115 μL, 0.69 mmol) in anhydrous DCM (1 mL) was added. The reaction mixture was stirred for 1 hour is at RT and then poured on a silica column (30 g, wet with c-Hex/EtOAc 4:1). Purification was performed with a gradient cHex/EtOAc 4:1 to c-Hex/EtOAc 1:1 in 30 min to give 158 mg of a white powder. Recrystallization from iPrOH gave 112 mg (43%) of the title compound as a white powder. HPLC, Rt: 3.02 min (purity: 99.0%). LC/MS, M+(ESI): 405.3. 1H NMR (CD3OD, 300 MHz) δ 7.00 (d, J=9.2 Hz, 2H), 6.89 (d, J=9.2 Hz, 2H), 4.56 (d, J=8.7 Hz, 1H), 3.87 (m, 3H), 3.78 (s, 3H), 3.73 (m, 1H), 3.50 (m, 1H), 3.15-3.00 (m, 4H), 1.93-1.72 (m, 2H), 1.66 (s, 3H), 1.58 (m, 1H), 1.56 (s, 3H), 0.98 (d, J=6.4 Hz, 6H).

Workup

  1. stirringThe reaction mixture was stirred for 1 hour
  2. customis at RT
  3. customPurification
  4. waitwas performed with a gradient cHex/EtOAc 4:1 to c-Hex/EtOAc 1:1 in 30 min

Sources & evidence

ORD record
ord-ac9728ea6e2b469192b93183d898355f
Source dataset
uspto-grants-2012_08
Patent number
US08247437B2

Reaction notes

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