Water → HCID 86694778, compound

HRID 709144Notes

Reaction equation

HRID 709144 reaction equation
[Cl:1]S([N:5]=[C:6]=[O:7])(=O)=O.[OH:8][CH2:9][C@H:10]([NH:22]C(=O)OC(C)(C)C)[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1.O>C(#N)C>[ClH:1].[C:6](=[O:7])([O:8][CH2:9][C@H:10]([NH2:22])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:21])[F:19])[CH:13]=1)[NH2:5]

Participants

5

Reactant 3

HCID 962WaterHCID 70918Chlorosulfonyl isocyanateHCID 69234882HCID 69234882, compound

Product 1

HCID 86694778HCID 86694778, compoundYield 22.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

At −15° C., 38 μl (0.44 mmol) of chlorosulphonyl isocyanate were added slowly to a solution of 100 mg (0.31 mmol) of (2R)-tert-butyl {1-hydroxy-3-[3-(trifluoromethyl)phenyl]propan-2-yl}carbamate (for the preparation see US patent application 2008/0242694, Example [0440]) in 2 ml of acetonitrile. The reaction mixture was stirred at RT for 1 h, 3 ml of water were then added and the mixture was heated under reflux overnight. After cooling to RT, the mixture was purified directly by preparative HPLC [Method 9]. This gave a first fraction (21 mg) of the title compound (in part as formate salt) and a fraction (17 mg) of the corresponding compound which was still Boc-protected. The latter fraction was stirred for 30 min with 3 ml of a 4 N solution of hydrogen chloride in dioxane and then freed from the volatile components on a rotary evaporator and then under high vacuum. The residue (16 mg) corresponded to the pure title compound. Both fractions of the title compound were combined and used to prepare subsequent compounds.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux overnight
  3. temperatureAfter cooling to RT
  4. customthe mixture was purified directly by preparative HPLC [Method 9]

Sources & evidence

ORD record
ord-5578368188c84420837498fbdce01679
Source dataset
uspto-grants-2015_11
Patent number
US09180120B2

Reaction notes

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