4-(Heptyloxy)benzoyl chloride → (S)-4-(2-(((benzyloxy)carbonyl)amino)-3-(tert-butoxy)-3-oxopropyl)phenyl 4-(heptyloxy)benzoate

HRID 1889155Notes

Reaction equation

HRID 1889155 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=1)[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:28]([O:35][C:36]1[CH:44]=[CH:43][C:39]([C:40](Cl)=[O:41])=[CH:38][CH:37]=1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>C(Cl)Cl.C(#N)C>[CH2:28]([O:35][C:36]1[CH:37]=[CH:38][C:39]([C:40]([O:27][C:24]2[CH:23]=[CH:22][C:21]([CH2:20][C@H:12]([NH:11][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[O:10])[C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])=[CH:26][CH:25]=2)=[O:41])=[CH:43][CH:44]=1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]

Participants

5

Reactant 2

HCID 27241824-(Heptyloxy)benzoyl chlorideHCID 11428694Z-Tyr-OtBu

Product 1

HCID 58545694(S)-4-(2-(((benzyloxy)carbonyl)amino)-3-(tert-butoxy)-3-oxopropyl)phenyl 4-(heptyloxy)benzoateYield 93%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Prepared using General Procedure 3: To a stirred solution of (S)-tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4-hydroxyphenyl)propanoate (5.57 g, 15.0 mmol) and TEA (6.27 mL, 45.0 mmol) in DCM (15 mL) and acetonitrile (30 mL) was added 4-(heptyloxy)benzoyl chloride (3.78 mL, 15.75 mmol) dropwise. After stirring overnight, the mixture was quenched with saturated aqueous NaHCO3 (50 mL). The organic layer was dried over MgSO4, and concentrated. The product was purified by chromatography (EA/hexanes) to afford 8.19 g (93%) of (S)-4-(2-(((benzyloxy)carbonyl)amino)-3-(tert-butoxy)-3-oxopropyl)phenyl 4-(heptyloxy)benzoate INT-4. LCMS-ESI (m/z) calculated for C35H43NO7: 589; no mass ion observed, tR=5.26 min (Method 3). 1H NMR (400 MHz, CDCl3) δ 8.17-8.08 (m, 2H), 7.41-7.28 (m, 5H), 7.19 (d, J=8.4 Hz, 2H), 7.15-7.07 (m, 2H), 7.01-6.91 (m, 2H), 5.35-5.23 (m, 1H), 5.17-5.04 (m, 2H), 4.54 (dd, J=13.9, 6.1 Hz, 1H), 4.04 (t, J=6.6 Hz, 2H), 3.10 (d, J=5.9 Hz, 2H), 1.91-1.76 (m, 2H), 1.47 (ddd, J=15.2, 8.9, 6.7 Hz, 2H), 1.43-1.36 (m, 10H), 1.36-1.30 (m, 5H), 0.90 (t, J=6.9 Hz, 3H).

Workup

  1. customPrepared
  2. customthe mixture was quenched with saturated aqueous NaHCO3 (50 mL)
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. customThe product was purified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-e68e2bd187044994a80b06dd9e2641a4
Source dataset
uspto-grants-2013_08
Patent number
US08501982B2

Reaction notes

Loading…