Di-tert-butyl dicarbonate → HCID 11974441, compound

HRID 1172348Notes

Reaction equation

HRID 1172348 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:14][C:13]([C:15]([OH:17])=[O:16])=[CH:12][CH2:11][C@H:10]1[C:18]1[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=1[F:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27][Si](C=[N+]=[N-])(C)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(=O)(O)[O-].[Na+]>CO.C(Cl)Cl.C(O)(=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][C:13]([C:15]([O:17][CH3:27])=[O:16])=[CH:12][CH2:11][C@@H:10]1[C:18]1[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:19]=1[F:26])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 90495Di-tert-butyl dicarbonateHCID 167693TrimethylsilyldiazomethaneHCID 516892Sodium BicarbonateHCID 68769741HCID 68769741, compound

Product 1

HCID 11974441HCID 11974441, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Alternative resolution procedure: A solution of Example 39A (510 mg) was dissolved in methanol (1 mL) and CH2Cl2 (1 mL), and then (trimethylsilyl)diazomethane solution (0.4 mL, 2M in ether) was added. After ten minutes, acetic acid (0.2 mL) was added. The resultant solution was concentrated in vacuo and partitioned between ethyl acetate and bicarb. The organic extract was washed with brine and dried over sodium sulfate. The crude material was deprotected using the procedure of Step B in Example 20D; and the product was partitioned between sodium bicarbonate and ethyl acetate. The organic phase was washed with brine and dried over sodium sulfate. The crude product (410 mg) was dissolved in 30 ml of ethanol. 420 mg (0.8 eq) of dibenzoyl (D)-tartaric acid was added, and the mixture was stirred until homogeneous. The resultant solution was allowed to stand overnight and the crystalline product was collected by filtration (yield 39%, ee>98%). The crystalline solid was dissolved in tetrahydrofuran (10 mL). Then, di-tert-butyl dicarbonate (1.1 eq.) and saturated sodium bicarbonate solution (5 mL) were added. After thirty minutes, the reaction mixture was concentrated and subjected to column chromatography (eluting with 20% ethyl acetate/hexane) to give the title compound.

Workup

  1. waitAfter ten minutes
  2. concentrationThe resultant solution was concentrated in vacuo
  3. custompartitioned between ethyl acetate and bicarb
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over sodium sulfate
  7. customand the product was partitioned between sodium bicarbonate and ethyl acetate
  8. washThe organic phase was washed with brine
  9. dry with materialdried over sodium sulfate
  10. dissolutionThe crude product (410 mg) was dissolved in 30 ml of ethanol
  11. filtrationthe crystalline product was collected by filtration (yield 39%, ee>98%)
  12. dissolutionThe crystalline solid was dissolved in tetrahydrofuran (10 mL)
  13. waitAfter thirty minutes
  14. concentrationthe reaction mixture was concentrated
  15. washsubjected to column chromatography (eluting with 20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-7e0e2424988d44a49aa66042b759d942
Source dataset
uspto-grants-2010_11
Patent number
US07834012B2

Reaction notes

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