1,2-Dichloroethane → HCID 57888787, compound

HRID 1016148Notes

Reaction equation

HRID 1016148 reaction equation
[NH2:1][C@H:2]([CH:21]([CH3:23])[CH3:22])[C:3]([N:5]1[CH2:10][CH2:9][C@@:8]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)([OH:11])[C:7]([CH3:20])([CH3:19])[CH2:6]1)=[O:4].[CH3:24][N:25]1[C:29]([C@@H:30]2[CH2:35][CH2:34][CH2:33][C@H:32]([C:36](O)=[O:37])[CH2:31]2)=[N:28][N:27]=[N:26]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)CC)C>C(Cl)Cl>[Cl:18][C:15]1[CH:14]=[CH:13][C:12]([C@@:8]2([OH:11])[CH2:9][CH2:10][N:5]([C:3](=[O:4])[C@H:2]([NH:1][C:36]([C@H:32]3[CH2:33][CH2:34][CH2:35][C@@H:30]([C:29]4[N:25]([CH3:24])[N:26]=[N:27][N:28]=4)[CH2:31]3)=[O:37])[CH:21]([CH3:23])[CH3:22])[CH2:6][C:7]2([CH3:19])[CH3:20])=[CH:17][CH:16]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 57889325HCID 57889325, compoundHCID 67299544HCID 67299544, compound

Product 1

HCID 57888787HCID 57888787, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-2-Amino-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methylbutan-1-one (25 mg, 0.067 mmol), (±)-cis-3-(1-methyl-1H-tetrazol-5-yl)cyclohexanecarboxylic acid (17 mg, 0.080 mmol), HOBT (12 mg, 0.080 mmol), EDC (15 mg, 0.080 mmol) and triethylamine (0.019 mL, 0.133 mmol) were mixed in methylene chloride (3 mL) at 25° C. with stirring. The reaction was stirred for 20 hours then washed with sat'd sodium bicarbonate. The methylene chloride layer was dried over sodium sulfate and concentrated in vacuo to give a white glass which was purified over silica gel (1:1 Hexanes/EtOAc to 100% EtOAc to 4:1 methylene chloride) to obtain (±)-cis-N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-(1-methyl-1H-tetrazol-5-yl)cyclohexanecarboxamide (35 mg, 0.066 mmol, 99% yield) as a white glass. MS found: (M+H)=531.46.

Workup

  1. stirringThe reaction was stirred for 20 hours
  2. washthen washed with sat'd sodium bicarbonate
  3. dry with materialThe methylene chloride layer was dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customto give a white glass which
  6. customwas purified over silica gel (1:1 Hexanes/EtOAc to 100% EtOAc to 4:1 methylene chloride)

Sources & evidence

ORD record
ord-5ff5911b3a014e5f9a45b4bf63949200
Source dataset
uspto-grants-2011_07
Patent number
US07985861B2

Reaction notes

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