Acetic Acid → HCID 10881559, compound

HRID 1604724Notes

Reaction equation

HRID 1604724 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([CH2:20][C:21]2([C:27]([O:29][CH3:30])=[O:28])[O:26][C:24](=[O:25])[CH2:23][CH2:22]2)=[CH:12]1.C(C1C=CC(S([N:43]=[N+:44]=[N-:45])(=O)=O)=C(C(C)C)C=1C(C)C)(C)C.C(O)(=O)C>C1COCC1>[N:43]([CH:23]1[CH2:22][C:21]([CH2:20][C:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[NH:11][CH:12]=2)([C:27]([O:29][CH3:30])=[O:28])[O:26][C:24]1=[O:25])=[N+:44]=[N-:45]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2733832Lithium HexamethyldisilazideHCID 11011159HCID 11011159, compoundHCID 21955793HCID 21955793, compound

Product 1

HCID 10881559HCID 10881559, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of LHMDS (1.0 M, 24.2 mL, 24.2 mmol) in THF was added indole lactone 11 (3.00 g, 11 mmol) in freshly distilled THF (33 mL) at -78° C. The light yellow solution was stirred for 40 min, and triisopropylbenzenesulfonyl azide (3.40 g, 11 mmol) in 33 mL dry THF was added at -78° C. via syringe. The reaction mixture was stirred for 20 min before quenching with acetic acid (49.5 mmol, 2.83 mL). The reaction mixture was allowed to warm to room temperature over 30 min before being diluted with saturated NH4C1 solution. This solution was stirred for 5 min and extracted with EtOAc (2×75 mL). The combined organic layers were dried (MgSO4), and the solvent was removed under reduced pressure. The crude oil was flash chromatographed on silica gel (1:2, EtOAc-hexanes eluant) to afford 2.21 g (64%) of pure azido lactone 12 as a mixture of diastereomers (3:2; SS/RR:SR/RS). A sample was crystallized from ethyl acetate/hexanes: mp. 110-112° C., SS/RR recemate; 1H NMR (300 MHz, CDC13) δ 2.19 (dd, 1H, J=14.0, 7.3 Hz), 2.63 (dd, 1H, J=14.0, 9.3 Hz), 3.34 (dd, 1H, J=9.0, 2.6 Hz), 3.39 (ABq, 2H, J=15.3 Hz), 3.84 (s, 3H), 7.10 (d, J=2.4 Hz), 7.14-7.24 ((m, 2H), 7.37 (d, 1H, J=8.3 Hz), 7.63 (d, 1H, J=7.6 Hz), 8.32 (brs 1H, D2O Exchangeable).

Workup

  1. stirringThe reaction mixture was stirred for 20 min
  2. additionbefore being diluted with saturated NH4C1 solution
  3. stirringThis solution was stirred for 5 min
  4. extractionextracted with EtOAc (2×75 mL)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. customthe solvent was removed under reduced pressure
  7. customchromatographed on silica gel (1:2, EtOAc-hexanes eluant)

Sources & evidence

ORD record
ord-4d1470a554624ec386a3d6e1f05306ee
Source dataset
uspto-grants-1999_11
Patent number
US05994559

Reaction notes

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