Acetic Acid → HCID 59312672, compound

HRID 1931557Notes

Reaction equation

HRID 1931557 reaction equation
[CH3:1][C@@H:2]([C@:6]1([CH3:51])[C@@H:45]([C:46]([OH:48])=[O:47])[C@@:44]2([CH3:49])[C@@:9]([CH3:50])([C@@H:10]3[C:41](=[CH:42][CH2:43]2)[C@@:14]24[CH2:21][C@@H:20]([N:22]5[C:26]([C:27]6[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=6)=[N:25][CH:24]=[N:23]5)[C@H:19]([O:33][CH2:34][C@@H:35]5[CH2:39][CH2:38][CH2:37][NH:36]5)[C@@:18]([CH3:40])([C@@H:13]2[CH2:12][CH2:11]3)[CH2:17][O:16][CH2:15]4)[CH2:8][CH2:7]1)[CH:3]([CH3:5])[CH3:4].C=O.[CH3:54]C(O)=O.C([BH3-])#N.[Na+]>CO.C1COCC1>[CH3:1][C@@H:2]([C@:6]1([CH3:51])[C@@H:45]([C:46]([OH:48])=[O:47])[C@@:44]2([CH3:49])[C@@:9]([CH3:50])([C@@H:10]3[C:41](=[CH:42][CH2:43]2)[C@@:14]24[CH2:21][C@@H:20]([N:22]5[C:26]([C:27]6[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=6)=[N:25][CH:24]=[N:23]5)[C@H:19]([O:33][CH2:34][C@@H:35]5[CH2:39][CH2:38][CH2:37][N:36]5[CH3:54])[C@@:18]([CH3:40])([C@@H:13]2[CH2:12][CH2:11]3)[CH2:17][O:16][CH2:15]4)[CH2:8][CH2:7]1)[CH:3]([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 59312578HCID 59312578, compound

Product 1

HCID 59312672HCID 59312672, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-8-[(1R)-1,2-dimethylpropyl]-14-[5-(4-pyridinyl)-1H-1,2,4-triazol-1-yl]-15-[(2S)-2-pyrrolidinylmethoxy]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid (Example 304; 98 mg, 0.14 mmol) in MeOH (6.0 mL) were added sequentially 30% (wt/wt) aqueous formaldehyde (126 mg, 4.21 mmol), HOAc (200 μL) and sodium cyanoborohydride in (448 μL of a 1.0 M solution in THF, 0.45 mmol). The reaction mixture was stirred at room temperature for 5 hours and then concentrated under reduced pressure. The residue was partitioned between CH2Cl2 and water and this mixture was extracted with 10% i-PrOH in CH2Cl2. The combined organic extracts were then dried with Na2SO4 and concentrated under reduced pressure. The residue was purified by RP HPLC (0.1% TFA water/methanol gradient) to provide the title compound (38 mg, 38%) as a white powder.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was partitioned between CH2Cl2 and water
  3. extractionthis mixture was extracted with 10% i-PrOH in CH2Cl2
  4. dry with materialThe combined organic extracts were then dried with Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by RP HPLC (0.1% TFA water/methanol gradient)

Sources & evidence

ORD record
ord-42803942ab284260a903f05c24d79b12
Source dataset
uspto-grants-2012_05
Patent number
US08188085B2

Reaction notes

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