(2S)-1,1,1-Trifluoropropan-2-ol → HCID 86684905, compound

HRID 2402896Notes

Reaction equation

HRID 2402896 reaction equation
[F:1][C:2]([F:7])([F:6])[C@@H:3]([OH:5])[CH3:4].CC(C)([O-])C.[Na+].[Cl:14][C:15]1[CH:20]=[C:19](F)[CH:18]=[CH:17][C:16]=1[S:22][C:23]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CC(N(C)C)=O.[Cl-].[Na+].O.C(O)C.O>[Cl:14][C:15]1[CH:20]=[C:19]([O:5][C@@H:3]([CH3:4])[C:2]([F:7])([F:6])[F:1])[CH:18]=[CH:17][C:16]=1[S:22][C:23]([C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)([C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

8

Reactant 3

HCID 6999971(2S)-1,1,1-Trifluoropropan-2-olHCID 23676156Sodium t-butoxideHCID 86684904HCID 86684904, compound

Product 1

HCID 86684905HCID 86684905, compoundYield 97%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 31374DimethylacetamideSolvent3×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
2 °C

Procedure

(S)-1,1,1-Trifluoro-propan-2-ol (100 g, 877 mmol) was dissolved in dimethylacetamide (600 mL) and the solution was cooled to 2° C. (ice bath). A solution of sodium tert-butoxide (77.5 g, 790 mmol) in dimethylacetamide (100 mL) was added at 2° C. and the mixture was stirred for 15 min. This solution was treated with a solution of 2-chloro-4-fluoro-1-tritylsulfanyl-benzene (200 g, 494 mmol) in dimethylacetamide (100 mL) at room temperature and subsequently stirred for 3 h at 50° C. It was then poured into a mixture of brine (200 mL), ice (1.2 kg) and water (2.0 L), and extracted with tert-butyl-methylether (2×1000 mL). The combined organic extracts were washed with brine/water 1:1 (v/v, 300 mL) and concentrated in vacuo to give the crude product as a yellow viscous oil. The oil was dissolved in ethanol (1.6 L), before water (240 mL) was slowly added at room temperature. The resulting suspension was stirred for 14 h, cooled to 2° C. (ice bath) and stirred for another 2 h, before it was filtered. The solid was washed with ethanol/water 4:1 (v/v, 500 mL) and dried in vacuo to afford the title compound as a white crystalline solid (238 g, 97%). 1H NMR (CDCl3, 400 MHz): δ 1.43 (d, J=6.5 Hz, 3H), 4.50 (qq, J=6.2 Hz, 6.2 Hz, 1H), 6.44 (dd, J=2.8 Hz, 8.7 Hz, 1H), 6.84 (d, J=2.7 Hz, 1H), 6.90 (d, J=8.6 Hz, 1H), 7.18-7.27 (m, 9H), 7.33-7.39 (m, 6H).

Workup

  1. stirringsubsequently stirred for 3 h at 50° C
  2. extractionextracted with tert-butyl-methylether (2×1000 mL)
  3. washThe combined organic extracts were washed with brine/water 1:1 (v/v, 300 mL)
  4. concentrationconcentrated in vacuo
  5. customto give the crude product as a yellow viscous oil
  6. additionwas slowly added at room temperature
  7. stirringThe resulting suspension was stirred for 14 h
  8. temperaturecooled to 2° C. (ice bath)
  9. stirringstirred for another 2 h, before it
  10. filtrationwas filtered
  11. washThe solid was washed with ethanol/water 4:1 (v/v, 500 mL)
  12. customdried in vacuo

Sources & evidence

ORD record
ord-2e693af83f7949a9be3390c975f23869
Source dataset
uspto-grants-2014_08
Patent number
US08796471B2

Reaction notes

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