Triethylamine → HCID 67437172, compound

HRID 1968886Notes

Reaction equation

HRID 1968886 reaction equation
Cl.[F:2][C:3]1[CH:4]=[CH:5][C:6]([C@@H:9]2[CH2:11][C@H:10]2[C:12]([OH:14])=O)=[N:7][CH:8]=1.[C:15]([O:19][C:20](=[O:43])[NH:21][C@H:22]([CH2:27][NH:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])=[CH:31][CH:30]=1)[C@@H:23]([CH3:26])[CH2:24][CH3:25])([CH3:18])([CH3:17])[CH3:16].C(N(CC)CC)C>S(Cl)(Cl)=O.C(Cl)Cl>[C:15]([O:19][C:20](=[O:43])[NH:21][C@H:22]([CH2:27][N:28]([C:29]1[CH:30]=[CH:31][C:32]([O:35][Si:36]([C:39]([CH3:40])([CH3:42])[CH3:41])([CH3:37])[CH3:38])=[CH:33][CH:34]=1)[C:12]([C@@H:10]1[CH2:11][C@H:9]1[C:6]1[CH:5]=[CH:4][C:3]([F:2])=[CH:8][N:7]=1)=[O:14])[C@@H:23]([CH3:26])[CH2:24][CH3:25])([CH3:17])([CH3:16])[CH3:18]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 67114485HCID 67114485, compoundHCID 67436438HCID 67436438, compound

Product 1

HCID 67437172HCID 67437172, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A mixture of trans-2-(5-fluoro-pyridin-2-yl)-cyclopropanecarboxylic acid HCl salt (217 mg, 1 mmol) in thionyl chloride (2 mL) was heated at reflux for over night. The mixture was concentrated and dried under high vacuum for 3 h. Then the residue was dissolved in DCM (4 mL) and added dropwise to a solution of ((1S,2S)-1-{[4-(t-butyl-dimethyl-silanyloxy)-phenylamino]-methyl}-2-methyl-butyl)-carbamic acid tert-butyl ester (422 mg, 1 mmol) and triethyl amine (409 uL, 3 mmol) in DCM (4 mL). The resulting mixture was stirred at rt for overnight. The reaction mixture was concentrated and the residue was subjected to ISCO (40 g column, 0-40% EtOAc in hexane over 40 min.) to give the titled compound (486 mg, 83%). MS (MH+ 586).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for over night
  3. concentrationThe mixture was concentrated
  4. customdried under high vacuum for 3 h
  5. dissolutionThen the residue was dissolved in DCM (4 mL)
  6. concentrationThe reaction mixture was concentrated
  7. customwas subjected to ISCO (40 g column, 0-40% EtOAc in hexane over 40 min.)

Sources & evidence

ORD record
ord-bcefcbcc7e5f4a40b15c79565ac74744
Source dataset
uspto-grants-2013_04
Patent number
US08426414B2

Reaction notes

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