Dimethyl Sulfide → HCID 58104610, compound
Reaction equation
C(OC(N1CC[C@H]([C@@H](C2CCCCC2)O)C1)=O)(C)(C)C.[C:21]([O:25][C:26]([N:28]1[CH2:32][CH2:31][C@H:30]([CH:33]=[O:34])[CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[F:45][C:46]1([F:55])[CH2:51][CH2:50][CH:49](C(Cl)=O)[CH2:48][CH2:47]1.S(C)C>C1COCC1>[C:21]([O:25][C:26]([N:28]1[CH2:32][CH2:31][CH:30]([CH:33]([CH:49]2[CH2:50][CH2:51][C:46]([F:55])([F:45])[CH2:47][CH2:48]2)[OH:34])[CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22]Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
The title compound was prepared in a manner similar to that described in Preparation 9 for the synthesis of (S)-3-((R)-cyclohexylhydroxymethyl) pyrrolidine-1-carboxylic acid t-butyl ester. (S)-3-Formylpyrrolidine-1-carboxylic acid t-butyl ester and LiHMDS were dissolved in THF under nitrogen and cooled at −78° C. 4,4-Difluoro-cyclohexanecarbonyl chloride (prepared by treatment of 4,4-difluorocyclohexane carboxylic acid with thionyl chloride in THF at 50° C. for 2 hours), was then added and the resulting mixture was stirred at −78° C. then allowed to reach room temperature overnight. BH3.Me2S in THF was added and the resulting mixture stirred at room temperature for 1 hour, then refluxed for 1 hour. The solids (1.03 g) were separated and dissolved in 1:1 AcOH:H2O (20 mL) and purified by preparative HPLC (BDS, 40-60%). This was repeated twice to yield:
Workup
- stirringthe resulting mixture stirred at room temperature for 1 hour
- temperaturerefluxed for 1 hour
- customThe solids (1.03 g) were separated
- dissolutiondissolved in 1:1 AcOH
- customH2O (20 mL) and purified by preparative HPLC (BDS, 40-60%)
Sources & evidence
- ORD record
- ord-f3c9726516b545adaa319802a0c44634
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09227933B2
Reaction notes
Loading…