Diisopropylethylamine → HCID 86655583, compound

HRID 39283

Reaction equation

HRID 39283 reaction equation
[C:1]([O:5][C:6]1[CH:11]=[C:10]([CH3:12])[C:9]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH:18]([P:25]([CH2:29][CH3:30])([CH2:27][CH3:28])=[O:26])[P:19]([CH2:23][CH3:24])([CH2:21][CH3:22])=[O:20])=[C:8]([CH3:31])[C:7]=1[CH2:32][CH2:33][C:34](O)=[O:35])(=[O:4])[CH2:2][CH3:3].[CH3:37]CN(C(C)C)C(C)C.C([O:50][C:51](=[O:61])[C@H:52]([CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)[NH2:53])(C)(C)C.CN(C(ON1N=N[C:72]2[CH:73]=[CH:74][CH:75]=[CH:76][C:71]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[CH2:37]([N:53]([C:34](=[O:35])[CH2:33][CH2:32][C:7]1[C:8]([CH3:31])=[C:9]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][CH:18]([P:19]([CH2:23][CH3:24])([CH2:21][CH3:22])=[O:20])[P:25]([CH2:27][CH3:28])([CH2:29][CH3:30])=[O:26])[C:10]([CH3:12])=[CH:11][C:6]=1[O:5][C:1](=[O:4])[CH2:2][CH3:3])[C@H:52]([C:51]([OH:50])=[O:61])[CH2:54][C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1)[C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 6931633tert-butyl (2S)-2-amino-3-phenylpropanoateHCID 86655581HCID 86655581, compound

Product 1

HCID 86655583HCID 86655583, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of acid 134 (221 mg, 0.363 mmol) in DMF (3 mL) at 0° C. was added DIEA (127 μL, 0.726 mmol) and L-phenylalanine t-Butyl ester (94 mg, 0.36 mmol). After stirring for 15 min at 0° C., HBTU (138 mg, 0.363 mmol) was added and stirring was continued for 2 hr at 0° C. then 2 hr at room temperature. The reaction mixture was diluted with EtOAc and washed with cold aqueous NaHSO4 (10%), H2O and saturated aqueous NaCl then dried over Na2SO4. The crude product was purified by silica gel chromatography (0 to 20% gradient of MeOH in CH2Cl2, 10 CV) using a Biotage Horizons™ system. Compound 135 was obtained as a pale yellow coloured liquid (276 mg, 94%). 1H NMR (400 MHz, CDCl3) δ 1.24 (t, J=7.5, 3H), 1.34 (t, J=7.1, 12H), 1.40 (s, 9H), 1.76-1.79 (m, 4H), 1.93-2.06 (m, 2H), 2.19-2.30 (m, 2H), 2.21 (s, 3H), 2.22 (s, 3H), 2.31 (tt, J=5.9, 24.2, 1H), 2.57 (q, J=7.5, 2H), 2.76-2.82 (m, 2H), 3.06 (bd, J=6.3, 2H), 3.67 (bd, J=5.9, 2H), 4.13-4.22 (m, 8H), 4.74 (dt, J=5.9, 7.6, 1H), 5.86 (d, J=7.5, 1H), 6.68 (s, 1H), 7.06-7.08 (m, 2H), 7.21-7.25 (m, 3H): 31P (162 MHz, CDCl3) δ 24.93 (s, 2P).

Workup

  1. stirringstirring
  2. waitwas continued for 2 hr at 0° C.
  3. custom2 hr
  4. customat room temperature
  5. washwashed with cold aqueous NaHSO4 (10%), H2O and saturated aqueous NaCl
  6. dry with materialthen dried over Na2SO4
  7. customThe crude product was purified by silica gel chromatography (0 to 20% gradient of MeOH in CH2Cl2, 10 CV)

Sources & evidence

ORD record
ord-7a62b611ad324492b64a4ce12c3d9c52
Source dataset
uspto-grants-2013_09
Patent number
US08524691B2

Linked notes

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