HCID 86695269, compound → HCID 86695267, compound

HRID 1504105Notes

Reaction equation

HRID 1504105 reaction equation
[CH2:1]([C:3]1([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:8][CH2:7][CH:6]([O:9][C:10]2[N:11]=[CH:12][N:13]=[C:14]3[C:21]=2[C:20]2[C@@H:19]([CH2:22][CH:23]=[O:24])[CH2:18][CH2:17][C:16]=2[S:15]3)[CH2:5][CH2:4]1)[CH3:2].C[Mg+].[Br-].[CH2:36]1COCC1>O1CCCC1>[CH2:1]([C:3]1([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:4][CH2:5][CH:6]([O:9][C:10]2[N:11]=[CH:12][N:13]=[C:14]3[C:21]=2[C:20]2[C@@H:19]([CH2:22][C@H:23]([OH:24])[CH3:36])[CH2:18][CH2:17][C:16]=2[S:15]3)[CH2:7][CH2:8]1)[CH3:2].[CH2:1]([C:3]1([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:4][CH2:5][CH:6]([O:9][C:10]2[N:11]=[CH:12][N:13]=[C:14]3[C:21]=2[C:20]2[C@@H:19]([CH2:22][C@@H:23]([OH:24])[CH3:36])[CH2:18][CH2:17][C:16]=2[S:15]3)[CH2:7][CH2:8]1)[CH3:2]

Participants

5

Reactant 2

HCID 86695269HCID 86695269, compoundHCID 178420625HCID 178420625, compound

Product 2

HCID 86695267HCID 86695267, compoundYield 47%HCID 86695268HCID 86695268, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Into a 100-mL round-bottom flask, purged and maintained under an inert atmosphere of nitrogen, was placed a solution of tert-butyl N-(1-ethyl-4-[[(3R)-3-(2-oxoethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]oxy]cyclohexyl)carbamate (330 mg, 0.72 mmol, 1.00 equiv) in 10 mL of distilled tetrahydrofuran. This solution was cooled to 0° C. Then CH3MgBr-THF (1 M, 1.5 mL) was added dropwise via syringe. The resulting solution was stirred for 2 h at this temperature. The reaction was then quenched by the addition of 10 mL of NH4Cl (aq.) and extracted with 3×50 mL of ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5) to give 160 mg (47%) of tert-butyl N-(1-ethyl-4-[[(3R)-3-[(2R)-2-hydroxypropyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]oxy]cyclohexyl)carbamate 199.2 as a white solid and 70 mg (20%) of tert-butyl N-(1-ethyl-4-[[(3R)-3-[(2S)-2-hydroxypropyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-12-yl]oxy]cyclohexyl)carbamate 199.1 as a white solid.

Workup

  1. customInto a 100-mL round-bottom flask, purged
  2. temperaturemaintained under an inert atmosphere of nitrogen
  3. customThe reaction was then quenched by the addition of 10 mL of NH4Cl (aq.)
  4. extractionextracted with 3×50 mL of ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-f2cba9cdfbe84004b4abce801de78f31
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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