1,2-Dichloroethane → tert-butyl (R)-1-((3S,4S)-4-(4-chlorophenyl)-3,4-dihydroxy-3-methylpiperidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate

HRID 238347Notes

Reaction equation

HRID 238347 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([OH:16])[CH2:13][CH2:12][NH:11][CH2:10][C@:9]2([CH3:15])[OH:14])=[CH:4][CH:3]=1.[C:17]([NH:24][C@@H:25]([C:29](O)=[O:30])[CH:26]([CH3:28])[CH3:27])([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].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:1][C:2]1[CH:7]=[CH:6][C:5]([C@@:8]2([OH:16])[CH2:13][CH2:12][N:11]([C:29](=[O:30])[C@H:25]([NH:24][C:17](=[O:18])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:26]([CH3:28])[CH3:27])[CH2:10][C@@:9]2([OH:14])[CH3:15])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 637605(2R)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoic acidHCID 59444285(3S,4S)-4-(4-chlorophenyl)-3-methylpiperidine-3,4-diol

Product 1

HCID 67968434tert-butyl (R)-1-((3S,4S)-4-(4-chlorophenyl)-3,4-dihydroxy-3-methylpiperidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamateYield 108.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of (3S,4S)-4-(4-chlorophenyl)-3-methylpiperidine-3,4-diol (91 g, 376 mmol), Boc-D-Valine (83.1 g, 382 mmol), HOBt (69.2 g, 452 mmol), EDC (87 g, 452 mmol) in CH2Cl2 (800 mL) and DMF (80 mL) was added DIPEA (132 mL, 753 mmol) at room temperature. The mixture was stirred at room temperature overnight. The reaction was concentrated and the residue partitioned between EtOAc and water. The EtOAc layer was washed with 1N HCl, sat. aq. NaHCO3, and brine to give the crude product (180 g, ˜80% purity) which was used directly in the next transformation.

Workup

  1. concentrationThe reaction was concentrated
  2. customthe residue partitioned between EtOAc and water
  3. washThe EtOAc layer was washed with 1N HCl, sat. aq. NaHCO3, and brine

Sources & evidence

ORD record
ord-78d2ad7d84b148b0b02fb1bae43c42c0
Source dataset
uspto-grants-2014_02
Patent number
US08642622B2

Reaction notes

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