Hydrochloric Acid → HCID 5358230, compound

HRID 2218494Notes

Reaction equation

HRID 2218494 reaction equation
[CH3:1][CH:2]1[CH:27]2[O:28][C:26]2([CH3:29])[CH:25]([O:30]C(CC(C)C)=O)[CH2:24][C:22](=[O:23])[N:21]([CH3:37])[C:14]2=[C:15]([Cl:20])[C:16]([O:18][CH3:19])=[CH:17][C:12](=[CH:13]2)[CH2:11][C:10]([CH3:38])=[CH:9][CH:8]=[CH:7][CH:6]([O:39][CH3:40])[C:5]2([OH:45])[NH:41][C:42]([O:44][CH:3]1[CH2:4]2)=[O:43].Cl.[Al]>C(OCC)(=O)C.O.O1CCCC1>[CH3:1][CH:2]1[CH:27]2[O:28][C:26]2([CH3:29])[CH:25]([OH:30])[CH2:24][C:22](=[O:23])[N:21]([CH3:37])[C:14]2=[C:15]([Cl:20])[C:16]([O:18][CH3:19])=[CH:17][C:12](=[CH:13]2)[CH2:11][C:10]([CH3:38])=[CH:9][CH:8]=[CH:7][CH:6]([O:39][CH3:40])[C:5]2([OH:45])[NH:41][C:42]([O:44][CH:3]1[CH2:4]2)=[O:43]

Participants

7

Reactant 3

HCID 313Hydrochloric Acid2×HCID 99958HCID 99958, compound2×HCID 5359268Aluminum

Product 1

HCID 5358230HCID 5358230, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-42 °C

Procedure

This example describes reduction of ansamitocins with LiAl(OMe)3H using water followed by aqueous HCl. Ansamitocins (200 mg, 0.32 mmol) were weighed into a 25 mL round bottomed flask. Tetrahydrofuran (1.0 mL) was added to the flask with stirring, and the flask was cooled in a −42° C. cooling bath. After 10 min, a solution of 0.67 M LiAl(OMe)3H in tetrahydrofuran (3.8 mL, 2.52 mmol) was added dropwise by syringe. The bath temperature was maintained between −34° C. and −42° C. throughout the addition. After addition was complete, the reaction was stirred for 2 hours at between −32° C. and −37° C. 1 mL of deionized water was added dropwise to the reaction. After a 30 min holding period, 2 mL of 3 M HCl and 10 mL of ethyl acetate were quickly added to the flask. The cooling unit was turned off, and most of the aluminum byproducts went into solution. The contents were transferred to a separatory funnel and mixed well. The organic layer was retained and washed with 2 mL of saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, and solvent was removed by rotary evaporation. The residue was purified by silica chromatography using a mobile phase of dichloromethane:methanol 95:5 (v:v) to give 117 mg of maytansinol (66% yield by weight).

Workup

  1. temperaturecooling bath
  2. temperatureThe bath temperature was maintained between −34° C. and −42° C. throughout the addition
  3. additionAfter addition
  4. stirringthe reaction was stirred for 2 hours at between −32° C. and −37° C
  5. waitAfter a 30 min holding period
  6. customThe contents were transferred to a separatory funnel
  7. additionmixed well
  8. washwashed with 2 mL of saturated sodium chloride
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate, and solvent
  10. customwas removed by rotary evaporation
  11. customThe residue was purified by silica chromatography

Sources & evidence

ORD record
ord-a966e17b8d8c46f5b87bb40feec6e530
Source dataset
uspto-grants-2008_08
Patent number
US07411063B2

Reaction notes

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