Water → HCID 11270195, compound

HRID 397215Notes

Reaction equation

HRID 397215 reaction equation
[Si:1]([O:8][C:9]1[C:10]2[C:26]3[C:17](=[C:18]4[C:23](=[CH:24][CH:25]=3)[NH:22][C:21]([CH3:28])([CH3:27])[CH:20]=[C:19]4[CH3:29])[C:16](=[O:30])[O:15][C:11]=2[CH:12]=[CH:13][CH:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C.O.CC#N>C1(C)C=CC=CC=1.CCCCCCC.CCOC(C)=O.CCCCCCC>[Si:1]([O:8][C:9]1[C:10]2[C:26]3[C:17](=[C:18]4[C:23](=[CH:24][CH:25]=3)[NH:22][C:21]([CH3:28])([CH3:27])[CH:20]=[C:19]4[CH3:29])[CH:16]([OH:30])[O:15][C:11]=2[CH:12]=[CH:13][CH:14]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 6342AcetonitrileHCID 11166097HCID 11166097, compoundHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 11270195HCID 11270195, compoundYield 110.5%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8900HeptaneSolventHCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
-78 °C

Procedure

The product from Example 1 (37.1 g) in toluene (1.8L) under N2 in a 3L 3-necked flask equipped with an overhead mechanical stirrer, addition funnel, and temperature probe was treated with diisobutylaluminum hydride in heptane (132 mL) dropwise at −78° C. over 40 minutes. After complete addition, the reaction mixture was stirred at −78° C. and monitored by HPLC, Zorbax Rx-C8 4.6 mm×25 cm column; mobile phase 90% H2O (0.1% H3PO4):10% CH3CN (0.1% H3PO4) to 30:70 over 15 minutes, then to 10:90 over 20 minutes before ramping back to 10:90 over 2 minutes; 45 minute run; flow rate of 1 mL/minute; UV detection at 225 nm. Retention times: starting material—29.9 minutes; product—20.4 minutes, and/or TLC, EtOAc:heptane (2:3), until starting material was consumed, about 1 hour. Ethyl acetate (500 mL) was added to quench any excess DIBAL, cooling was removed and saturated Rochelle's salt solution (1L) was added. The quenched mixture warmed to room temperature with stirring. The stirring was continued until layers clearly separated. The organic layer was washed with brine (500 mL) before concentrating to a solid. The isolated solid was dried at 40° C. in a vacuum oven to yield 41.2 g of the title compound as a tan solid which was used in the next step without further purification. A small reference sample was crystallized from CH3CN. Anal. calcd for C25H33NO3Si: C, 70.88; H, 7.85; N, 3.31. Found: C, 70.60; H, 7.84; N, 3.22; 1H NMR [(CD3)2SO] δ0.10 (3H, s), 0.97 (9H, s), 1.08 (3H, s), 1.26 (3H, s), 2.24 (3H, s), 5.41 (1H, br), 6.07 (1H, br),6.55˜6.61 (4H, m), 6.91(1H, d), 6.98 (1H, t), 7.99 (1H, d); 13C NMR [(CD3)2SO] δ−4.5, −4.2, 18.0,22.8, 25.8, 25.8, 28.2, 30.1, 49.7, 89.9, 111.2, 113.5, 113.7, 115.7, 116.4, 116.9, 126.2, 127.2, 128.2, 130.2, 132.4, 145.3, 151.0, 151.8 with 2 peaks overlapping; HRMS-FAB: calcd m/z 423.2230, found 423.2232.

Workup

  1. additionAfter complete addition
  2. custom45 minute
  3. custommaterial—29.9 minutes
  4. customwas consumed, about 1 hour
  5. additionEthyl acetate (500 mL) was added
  6. customto quench any excess DIBAL
  7. temperaturecooling
  8. customwas removed
  9. additionsaturated Rochelle's salt solution (1L) was added
  10. temperatureThe quenched mixture warmed to room temperature
  11. stirringwith stirring
  12. customclearly separated
  13. washThe organic layer was washed with brine (500 mL)
  14. concentrationbefore concentrating to a solid
  15. customThe isolated solid was dried at 40° C. in a vacuum oven

Sources & evidence

ORD record
ord-4098a688d81141ca9a70bff1577b1beb
Source dataset
uspto-grants-2003_08
Patent number
US06608216B2

Reaction notes

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