Triethylamine → 1,1-Dimethylethyl 4-[4-[[methyl[(1R)-1-phenylpropyl]amino]carbonyl]-2-thiazolyl]-1-piperidinecarboxylate

HRID 2043712Notes

Reaction equation

HRID 2043712 reaction equation
[C:1]([C:4]1[N:5]=[C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[S:7][CH:8]=1)([OH:3])=O.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.CC1C=CC(C)=CC=1CC(N1CCC(C2SC=C([C:75]([N:77](C)[C@@H:78]([C:81]3[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=3)[CH2:79][CH3:80])=O)N=2)CC1)=O>C(#N)C>[CH3:75][N:77]([C@@H:78]([C:81]1[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=1)[CH2:79][CH3:80])[C:1]([C:4]1[N:5]=[C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[S:7][CH:8]=1)=[O:3]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 27955312-(1-((Tert-butoxy)carbonyl)piperidin-4-yl)-1,3-thiazole-4-carboxylic acid2×HCID 674615172-[1-[(2,5-dimethylphenyl)acetyl]-4-piperidinyl]-N-methyl-N-[(1R)-1-phenylpropyl]-4-thiazolecarboxamide

Product 1

HCID 674615141,1-Dimethylethyl 4-[4-[[methyl[(1R)-1-phenylpropyl]amino]carbonyl]-2-thiazolyl]-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1-(1,1-Dimethylethyl) 4-(4-carboxy-2-thiazolyl)-1-piperidinecarboxylate (i.e. the product of Example 1, Step B) (3.1 g, 9.9 mmol) was suspended in 10 mL of dry acetonitrile and treated with triethylamine (3.0 mL, 21 mmol) to give a homogeneous solution. To this was added O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (3.98 g, 10.5 mmol) followed by (α,R)-α-ethyl-N-methylbenzenemethanamine (i.e. the product of Example 1, Step C) (10 mmol, 1.50 g). The mixture was stirred at ambient temperature for 4 days, concentrated under reduced pressure, diluted with ethyl acetate, washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine, dried over MgSO4 and concentrated under reduced pressure to give 5.1 g of a dark oil. Purification by silica gel chromatography using 25% ethyl acetate in hexanes gave 3.6 g of the title compound as a yellow oil.

Workup

  1. customto give a homogeneous solution
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with ethyl acetate
  4. washwashed with 1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-828105e7a65a46d88e01fe571fbf0f69
Source dataset
uspto-grants-2013_11
Patent number
US08586611B2

Reaction notes

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