Hydrochloric Acid → 2-[(3R)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl]ethan-1-ol

HRID 1503950Notes

Reaction equation

HRID 1503950 reaction equation
[Si]([O:8][CH2:9][CH2:10][C@H:11]1[CH2:22][CH2:21][C:20]2[S:19][C:18]3[N:17]=[CH:16][N:15]=[C:14]([O:23][CH:24]4[CH2:29][CH2:28][CH:27]([N:30]5[CH2:35][CH2:34][O:33][CH2:32][CH2:31]5)[CH2:26][CH2:25]4)[C:13]=3[C:12]1=2)(C(C)(C)C)(C)C.Cl>CO>[N:30]1([CH:27]2[CH2:26][CH2:25][CH:24]([O:23][C:14]3[C:13]4[C:12]5[C@@H:11]([CH2:10][CH2:9][OH:8])[CH2:22][CH2:21][C:20]=5[S:19][C:18]=4[N:17]=[CH:16][N:15]=3)[CH2:29][CH2:28]2)[CH2:31][CH2:32][O:33][CH2:34][CH2:35]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86695110(3R)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraene

Product 1

HCID 681155022-[(3R)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraen-3-yl]ethan-1-olYield 91%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (3R)-3-[2-[(tert-butyldimethylsilyl)oxy]ethyl]-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraene (850 mg, 1.64 mmol, 1.00 equiv) in methanol (20 mL) was added hydrochloric acid (2 M, 1.0 mL) and the resulting mixture was stirred for 1 hr at 0° C. in a water/ice bath. After completion, the reaction was quenched with sodium bicarbonate (sat.) and extracted with 3×80 mL of ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column with chloroform/methanol (15:1) to afford 2-[(3R)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]ethan-1-ol (600 mg, 91%) as a colorless oil. MS (ES): m/z 404 [M+H]+.

Workup

  1. customAfter completion, the reaction was quenched with sodium bicarbonate (sat.)
  2. extractionextracted with 3×80 mL of ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified on a silica gel column with chloroform/methanol (15:1)

Sources & evidence

ORD record
ord-7b91e9e41a7f42f988519f900a7ed540
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

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