1,2-Dichloroethane → HCID 54771495, compound

HRID 238349Notes

Reaction equation

HRID 238349 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]([OH:20])([CH3:19])[CH2:6]1)=[O:4].[F:24][C:25]1([F:33])[CH2:29][CH2:28][C@@H:27]([C:30](O)=[O:31])[CH2:26]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([C@@:8]2([OH:11])[CH2:9][CH2:10][N:5]([C:3](=[O:4])[C@H:2]([NH:1][C:30]([C@@H:27]3[CH2:28][CH2:29][C:25]([F:33])([F:24])[CH2:26]3)=[O:31])[CH:21]([CH3:23])[CH3:22])[CH2:6][C@@:7]2([OH:20])[CH3:19])=[CH:13][CH:14]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 67953936HCID 67953936, compoundHCID 67953940HCID 67953940, compound

Product 1

HCID 54771495HCID 54771495, compoundYield 99.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of (R)-2-amino-1-((3S,4S)-4-(4-chlorophenyl)-3,4-dihydroxy-3-methylpiperidin-1-yl)-3-methylbutan-1-one (22.49 g, 66.0 mmol), (R)-3,3-difluorocyclopentanecarboxylic acid (10.21 g, 68.0 mmol) in CH2Cl2 (300 mL) and DMF (75 mL) were added HOBT (12.50 g, 82 mmol), EDC (15.65 g, 82 mmol) and Hunig's base (23.76 mL, 136 mmol). The reaction was stirred for 20 h at rt then concentrated to remove the CH2Cl2. Ethyl acetate was added and the organic layer was washed twice with 1N HCl, twice with saturated sodium carbonate and three times with water. The organic layer was dried over sodium sulfate and concentrated to give a glass solid which was crystallized from CH3CN to give (R)—N—((R)-1-((3S,4S)-4-(4-chlorophenyl)-3,4-dihydroxy-3-methylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3,3-difluorocyclopentanecarboxamide (31.03 g, 65.6 mmol, 99% yield).

Workup

  1. concentrationthen concentrated
  2. customto remove the CH2Cl2
  3. additionEthyl acetate was added
  4. washthe organic layer was washed twice with 1N HCl, twice with saturated sodium carbonate and three times with water
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated
  7. customto give a glass solid which
  8. customwas crystallized from CH3CN

Sources & evidence

ORD record
ord-862df64d80154b458524f84c0b6b4933
Source dataset
uspto-grants-2014_02
Patent number
US08642622B2

Reaction notes

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