Triethylamine → Discodermolide

HRID 1634586Notes

Reaction equation

HRID 1634586 reaction equation
B(Cl)([C@@H]1[C@@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1)[C@@H]1[C@@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1.C(N(CC)CC)C.CC([Si](C)(C)[O:35][C@@H:36]([C@@H:45]([CH3:49])[C:46](=[O:48])[CH3:47])[C@@H:37]([CH3:44])[C:38](N(OC)C)=[O:39])(C)C.[NH2:52][C:53]([O:55][C@@H:56]([C@@H:91]([CH3:96])/[CH:92]=[CH:93]/[CH:94]=[CH2:95])[C@@H:57]([CH3:90])[C@H:58]([O:82][Si](C(C)(C)C)(C)C)[C@@H:59]([CH3:81])[CH2:60]/[C:61](/[CH3:80])=[CH:62]\[C@H:63]([CH3:79])[C@@H:64]([O:71][Si](C(C)(C)C)(C)C)[C@@H:65]([CH3:70])/[CH:66]=[CH:67]\[CH:68]=[O:69])=[O:54]>C(OCC)C>[CH3:49][C@@H:45]1[C@H:36]([OH:35])[C@@H:37]([CH3:44])[C:38](=[O:39])[O:48][C@H:46]1[CH2:47][C@H:68]([OH:69])/[CH:67]=[CH:66]\[C@@H:65]([C@H:64]([OH:71])[C@H:63](/[CH:62]=[C:61](\[CH2:60][C@@H:59]([C@@H:58]([OH:82])[C@@H:57]([C@@H:56]([O:55][C:53]([NH2:52])=[O:54])[C@H:91](/[CH:92]=[CH:93]\[CH:94]=[CH2:95])[CH3:96])[CH3:90])[CH3:81])/[CH3:80])[CH3:79])[CH3:70]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9923635(2R,3S,4R)-3-[tert-butyl(dimethyl)silyl]oxy-N-methoxy-N,2,4-trimethyl-5-oxohexanamideHCID 13515837Chlorobis(2,6,6-trimethylbicyclo(3.1.1)heptan-3-yl)boraneHCID 88097159HCID 88097159, compound

Product 1

HCID 643668Discodermolide

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2.18 g (6.79 mmol, 10 equiv.) of (+)-β-chlorodiisopinocamphenylborane in 4 mL of diethyl ether at 0° C. is added 1.04 mL (11 equiv., distilled over calcium hydride) of triethylamine and then a solution of 2.25 g (6.79 mmol, 10 equiv.) of the compound of Example 1 in 3 mL of diethylether. After stirring for 2 hours at 0° C., the mixture is cooled to −78° C., after which time a pre-cooled (−78° C.) solution of 450 mg (0.679 mmol) of (2Z,4S,5S,6S,7Z,10S,11R,12R,13S,14S,15E)-13-[(amino-carbonyl)oxyl]-5,11-bis[[(1,1-dimethylethyl)dimethylsilyl]oxy]-4,6,8,10,12,14-hexamethyl-2,7,15,17-octadecatetraenal in 4 mL of diethylether is added via cannula. After the resultant mixture is maintained at a temperature of −78° C. for 3 hours, it is transferred to a freezer (−27° C.) for 16 hours. The reaction is then quenched with 8 mL of methanol (the pH of which is adjusted to 7 with 12 mL of buffer solution) and 4 mL of 50% hydrogen peroxide solution at 0° C. After stirring for 2 hours at 25° C., the organic layers are separated. The aqueous layer is then extracted five times with 25 mL portions of dichloromethane. The combined organic layers are then dried over magnesium sulfate, concentrated using a rotary evaporator and chromatographed (Biotage, silica gel, gradient 10-30% ethyl acetate/hexane) to yield the desired compound as a colorless, highly viscous oil.

Workup

  1. temperaturethe mixture is cooled to −78° C.
  2. additionis added via cannula
  3. waitit is transferred to a freezer (−27° C.) for 16 hours
  4. customThe reaction is then quenched with 8 mL of methanol (the pH of which
  5. customat 0° C
  6. stirringAfter stirring for 2 hours at 25° C.
  7. customthe organic layers are separated
  8. extractionThe aqueous layer is then extracted five times with 25 mL portions of dichloromethane
  9. dry with materialThe combined organic layers are then dried over magnesium sulfate
  10. concentrationconcentrated
  11. customa rotary evaporator
  12. customchromatographed (Biotage, silica gel, gradient 10-30% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-c855473d93e649bc84aca93cb7f3b3b1
Source dataset
uspto-grants-2003_01
Patent number
US06506910B1

Reaction notes

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