HCID 86711172, compound → HCID 86711171, compound

HRID 876899Notes

Reaction equation

HRID 876899 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@@:26]3([CH2:47][C@H:21]2[C:20](=[O:48])[NH:19][C@:18]2([C:50]([O:52][CH2:53][CH3:54])=[O:51])[CH2:49][C@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[O:45][C:30]1[C:31]([C:41]([F:44])([F:43])[F:42])=[N:32][C:33]2[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][C:38]=2[C:29]=1[C:28](=[O:46])[CH2:27]3)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:55][Mg+].[Br-]>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:23](=[O:24])[N:22]2[CH2:25][C@@:26]3([CH2:47][C@H:21]2[C:20](=[O:48])[NH:19][C@:18]2([C:50]([O:52][CH2:53][CH3:54])=[O:51])[CH2:49][C@H:17]2[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[O:45][C:30]1[C:31]([C:41]([F:44])([F:42])[F:43])=[N:32][C:33]2[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][C:38]=2[C:29]=1[C:28]([OH:46])([CH3:55])[CH2:27]3)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 86711172HCID 86711172, compoundHCID 178418689HCID 178418689, compound

Product 1

HCID 86711171HCID 86711171, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-25 °C

Procedure

To the solution of (2S,6S,13aS,14aR,16aS,Z)-ethyl 6-((tert-butoxycarbonyl) amino)-9′-methoxy-1′,5,16-trioxo-5′-(trifluoromethyl)-1′,2′,3,5,6,7,8,9,10,11,13a,14,14a,15, 16,16a-hexadecahydro-1H-spiro[cyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-2,3′-pyrano[2,3-c]quinoline]-14a-carboxylate (2923 mg, 3.85 mmol) in THF (26 ml) was added 1.4M of MeMgBr solution in THF (11.01 ml, 15.41 mmol) at −25° C. and stirred at −25° C. for 20 min. TLC and LC-MS indicated that the major was product (about 50%) and starting material. Then the reaction was quenched with 1N HCl to pH=5-6 (about 12 ml 1N HCl), and diluted with EtOAc (40 ml). The layers were separated, and the aq. layer was extracted again with EtOAc (25 ml×2). The organic layers were combined and washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (120 g, gold column), eluting with 100% hexane for 400 ml, gradient to 35% of acetone to give 1430 mg of starting material and 1130 mg of (2S,6S,13aS,14aR,16aS,Z)-ethyl 6-((tert -butoxycarbonyl)amino)-1′-hydroxy-9′-methoxy-1′-methyl-5,16-dioxo-5′-(trifluoromethyl)-1′,2′,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydro-1H-spiro[cyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-2,3′-pyrano[2,3-c]quinoline]-14a-carboxylate as a light yellow solid. m/z=775.4 (M+1)

Workup

  1. customThen the reaction was quenched with 1N HCl to pH=5-6 (about 12 ml 1N HCl)
  2. additiondiluted with EtOAc (40 ml)
  3. customThe layers were separated
  4. extractionthe aq. layer was extracted again with EtOAc (25 ml×2)
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography on silica gel (120 g, gold column)
  10. washeluting with 100% hexane for 400 ml, gradient to 35% of acetone

Sources & evidence

ORD record
ord-9a5d22280dc5471182683dec003da12c
Source dataset
uspto-grants-2015_03
Patent number
US08987195B2

Reaction notes

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