Cyclobutanol → HCID 68707249, compound

HRID 2261918Notes

Reaction equation

HRID 2261918 reaction equation
[CH:1]1([OH:5])[CH2:4][CH2:3][CH2:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[C:16]([O:20][C:21]([NH:23][C@:24]([C:33]1[O:37][C:36]([C:38]2[CH:39]=[C:40]([N:46]([CH3:51])[S:47]([CH3:50])(=[O:49])=[O:48])[CH:41]=[C:42]([CH2:44]Br)[CH:43]=2)=[N:35][N:34]=1)([CH3:32])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:22])([CH3:19])([CH3:18])[CH3:17]>CN(C=O)C.O>[C:16]([O:20][C:21]([NH:23][C@:24]([C:33]1[O:37][C:36]([C:38]2[CH:39]=[C:40]([N:46]([CH3:51])[S:47]([CH3:50])(=[O:49])=[O:48])[CH:41]=[C:42]([CH2:44][O:5][CH:1]3[CH2:4][CH2:3][CH2:2]3)[CH:43]=2)=[N:35][N:34]=1)([CH3:32])[CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:22])([CH3:19])([CH3:18])[CH3:17]

Participants

6

Reactant 3

HCID 76218CyclobutanolHCID 2724254Sodium bis(trimethylsilyl)amideHCID 58990072HCID 58990072, compound

Product 1

HCID 68707249HCID 68707249, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of cyclobutanol (0.009 mL, 0.115 mmol) in 0.26 mL DMF, cooled to 0° C., was added sodium bis(trimethylsilyl)amide dropwise. After stirring for 5 min, a solution of 3-(5-((R)-2-tert-butoxycarbonylamino-1-phenylpropan-2-yl)-1,3,4-oxadiazol-2-yl)-5-(bromomethyl)-N-methyl-N-(methylsulfonyl)benzenamine (13.5 mg, 0.023 mmol) in 0.25 mL DMF was added and the reaction was stirred at 0° C. for 1 h. The reaction mixture was diluted with water, extracted with EtOAc and washed with brine. Drying, solvent evaporation and flash chromatography (15-55% EtOAc/hexanes) gave 3-(5-((R)-2-tert-butoxycarbonylamino-1-phenylpropan-2-yl)-1,3,4-oxadiazol-2-yl)-5-(cyclobutoxymethyl)-N-methyl-N-(methylsulfonyl)benzenamine. 1H NMR (CDCl3) δ 7.90 (d, J=9.0 Hz, 2H), 7.58 (s, 1H), 7.27 (m, 3H), 7.06 (m, 2H), 5.09 (bs, 1H), 4.47 (s, 2H), 4.05 (m, 1H), 3.57 (d, J=13.6 Hz, 1H), 3.43 (m, 1H), 3.38 (s, 3H), 2.90 (s, 3H), 2.24 (m, 2H), 2.02 (m, 2H), 1.73 (s, 3H), 1.56 (m, 2H), 1.42 (s, 9H).

Workup

  1. stirringthe reaction was stirred at 0° C. for 1 h
  2. extractionextracted with EtOAc
  3. washwashed with brine
  4. customDrying
  5. customsolvent evaporation and flash chromatography (15-55% EtOAc/hexanes)

Sources & evidence

ORD record
ord-97e790526021410a8e9804082b393383
Source dataset
uspto-grants-2010_12
Patent number
US07847100B2

Reaction notes

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