Dimethyl Sulfide → HCID 58104610, compound

HRID 1671388Notes

Reaction equation

HRID 1671388 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

7

Reactant 5

HCID 1068Dimethyl SulfideHCID 1514343(S)-tert-butyl 3-formylpyrrolidine-1-carboxylateHCID 2733832Lithium HexamethyldisilazideHCID 187583104,4-Difluorocyclohexane-1-carbonyl chlorideHCID 58104612HCID 58104612, compound

Product 1

HCID 58104610HCID 58104610, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

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

  1. stirringthe resulting mixture stirred at room temperature for 1 hour
  2. temperaturerefluxed for 1 hour
  3. customThe solids (1.03 g) were separated
  4. dissolutiondissolved in 1:1 AcOH
  5. customH2O (20 mL) and purified by preparative HPLC (BDS, 40-60%)

Sources & evidence

ORD record
ord-bffdbe6c70784c45979c9218a36e92f8
Source dataset
uspto-grants-2011_08
Patent number
US07994209B2

Reaction notes

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