p-Toluenesulfonic acid → HCID 68115506, compound

HRID 1503943Notes

Reaction equation

HRID 1503943 reaction equation
[CH3:1][N:2]([CH:10]1[CH2:15][CH2:14][CH:13]([O:16][C:17]2[C:28]3[C:27]4[C@@H:26]([CH2:29]C=O)[CH2:25][CH2:24][C:23]=4[S:22][C:21]=3[N:20]=[CH:19][N:18]=2)[CH2:12][CH2:11]1)[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].CO[CH:34]([O:37][CH3:38])[O:35][CH3:36].CC1C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:38][O:37][CH:34]([O:35][CH3:36])[CH2:29][C@H:26]1[CH2:25][CH2:24][C:23]2[S:22][C:21]3[N:20]=[CH:19][N:18]=[C:17]([O:16][CH:13]4[CH2:12][CH2:11][CH:10]([N:2]([CH3:1])[C:3](=[O:9])[O:4][C:5]([CH3:7])([CH3:6])[CH3:8])[CH2:15][CH2:14]4)[C:28]=3[C:27]1=2

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 86695117HCID 86695117, compound

Product 1

HCID 68115506HCID 68115506, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

For the preparation of the starting material compound 43.1, see Example 43. Into a 50-mL round-bottom flask containing a solution of tert-butyl N-methyl-N-(4-[[(3R)-3-(2-oxoethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)carbamate (460 mg, 1.03 mmol, 1.00 equiv) in methanol (15 mL) was added trimethoxymethane (548 mg, 5.16 mmol, 5.00 equiv) and 4-methylbenzene-1-sulfonic acid (18 mg, 0.10 mmol, 0.10 equiv) at room temperature under nitrogen. The reaction mixture was stirred for 4 hr at ambient temperature. After completion, the reaction was quenched with saturated aqueous NaHCO3 and extracted with 3×50 mL of ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column with ethyl acetate/petroleum ether (1:8) to afford the desired tert-butyl N-(4-[[(3R)-3-(2,2-dimethoxyethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (470 mg, 93%) as a colorless oil. LC-MS (ES): m/z 562 [M+H]+.

Workup

  1. customAfter completion, the reaction was quenched with saturated aqueous NaHCO3
  2. extractionextracted with 3×50 mL of ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified on a silica gel column with ethyl acetate/petroleum ether (1:8)

Sources & evidence

ORD record
ord-25cc9a9f4865412480728616e121dbcf
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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