1,2-Dichloroethane → Tert-butyl (2R,5S)-2-[(R)-hydroxy(phenyl)methyl]-5-(4-{[5-(1,3-thiazol-4-yl)piperidin-1-yl]carbonyl}benzyl)pyrrolidine-1-carboxylate

HRID 1804647Notes

Reaction equation

HRID 1804647 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@H:13]([OH:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:11][CH2:10][C@H:9]1[CH2:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([OH:28])=O)=[CH:24][CH:23]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[S:31]1[CH:35]=[C:34]([CH:36]2[CH2:41][CH2:40]NC[CH2:37]2)[N:33]=[CH:32]1.C1C=[N:46][C:45]2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[OH:20][C@H:13]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C@H:12]1[CH2:11][CH2:10][C@@H:9]([CH2:21][C:22]2[CH:30]=[CH:29][C:25]([C:26]([N:46]3[CH2:37][CH:36]([C:34]4[N:33]=[CH:32][S:31][CH:35]=4)[CH2:41][CH2:40][CH2:45]3)=[O:28])=[CH:24][CH:23]=2)[N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 392362494-(1,3-Thiazol-4-yl)piperidineHCID 670587074-({(2S,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl}methyl)benzoic acid

Product 1

HCID 86666756Tert-butyl (2R,5S)-2-[(R)-hydroxy(phenyl)methyl]-5-(4-{[5-(1,3-thiazol-4-yl)piperidin-1-yl]carbonyl}benzyl)pyrrolidine-1-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 4-{((2s,5R)-1-(tert-butoxycarbonyl)-5-[(R)-hydroxy(phenyl)methyl]pyrrolidin-2-yl)methyl}benzoic acid (82 mg, 0.2 mmol) and 4-(1,3-thiazol-4-yl)piperidine (30 mg, 0.2 mmol) in 1.5 mL anhydrous DMF was added a 0.5 M solution of HOAt in DMF (0.4 mL, 0.2 mmol) followed by EDC (78 mg, 0.4 mmol) and DIEA (70 μL, 0.4 mmol). The resulting mixture was stirred at RT under nitrogen atmosphere for 16 h. The mixture was washed with water and extracted with dichloromethane (2×5 mL). The organics were combined, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was purified by preparative TLC plate (1000 uM) eluting with 5% MeOH in dichloromethane to afford the product (91 mg, 88%). ESI-MS calculated for C32H39N3O4S: Exact Mass: 561.27. Found 562.28 (MH)+ and 584.28 (MNa)+.

Workup

  1. washThe mixture was washed with water
  2. extractionextracted with dichloromethane (2×5 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customThe residue was purified by preparative TLC plate (1000 uM)
  7. washeluting with 5% MeOH in dichloromethane

Sources & evidence

ORD record
ord-e2840b3b884f40059a477f3de0ca4f51
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

Loading…