p-Toluenesulphonyl cyanide → (R)-6,8-difluoro-3-[5-((R)-6-fluoro-3-pentylchroman-7-yl)-1,3-dioxan-2-yl]chroman-7-carbonitrile

HRID 2420645Notes

Reaction equation

HRID 2420645 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[CH:11]=1)[O:8][CH2:7][C@H:6]([CH:13]1[O:18][CH2:17][CH:16]([C:19]3[CH:28]=[C:27]4[C:22]([CH2:23][C@@H:24]([CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[CH2:25][O:26]4)=[CH:21][C:20]=3[F:34])[CH2:15][O:14]1)[CH2:5]2.C([Li])(CC)C.C1(C)C=CC(S([C:49]#[N:50])(=O)=O)=CC=1>C1COCC1.C1CCCCC1.CCOCC>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[C:11]=1[C:49]#[N:50])[O:8][CH2:7][C@H:6]([CH:13]1[O:18][CH2:17][CH:16]([C:19]3[CH:28]=[C:27]4[C:22]([CH2:23][C@@H:24]([CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[CH2:25][O:26]4)=[CH:21][C:20]=3[F:34])[CH2:15][O:14]1)[CH2:5]2

Participants

7

Reactant 3

HCID 87946p-Toluenesulphonyl cyanideHCID 59288368(R)-6,8-difluoro-3-[5-((R)-6-fluoro-3-pentylchroman-7-yl)-1,3-dioxan-2-yl]chromanHCID 178418400CID 53628100

Product 1

HCID 59288340(R)-6,8-difluoro-3-[5-((R)-6-fluoro-3-pentylchroman-7-yl)-1,3-dioxan-2-yl]chroman-7-carbonitrile

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Conditions

Temperature
-25 °C

Procedure

800 mg (1.68 mmol) of (R)-6,8-difluoro-3-[5-((R)-6-fluoro-3-pentylchroman-7-yl)-1,3-dioxan-2-yl]chroman are dissolved in 30 ml of THF, and 1.7 ml (2.38 mmol) of a 1.4 M solution of s-butyllithium in cyclohexane are added at −50° C. The batch is warmed at −25° C. for 5 min, left to stir at −70° C. for 2 h, and a solution of 400 mg (2.21 mmol) of p-toluenesulfonyl cyanide in 10 ml of THF is subsequently added at such a rate that the temperature does not exceed −65° C. After 1 h, the batch is allowed to thaw, diluted with ether and washed with dil. hydrochloric acid. The org. phase is dried over sodium sulfate and evaporated, and the crude product is chromatographed on silica gel with toluene, giving (R)-6,8-difluoro-3-[5-((R)-6-fluoro-3-pentylchroman-7-yl)-1,3-dioxan-2-yl]chroman-7-carbonitrile as colourless crystals of m.p. 111° C.

Workup

  1. waitleft
  2. customdoes not exceed −65° C
  3. waitAfter 1 h
  4. washwashed with dil. hydrochloric acid
  5. dry with materialphase is dried over sodium sulfate
  6. customevaporated
  7. customthe crude product is chromatographed on silica gel with toluene

Sources & evidence

ORD record
ord-b01dbb3303a74031b51a268f8fc25933
Source dataset
uspto-grants-2011_06
Patent number
US07955664B2

Reaction notes

Loading…