Benzoyl isothiocyanate → HCID 86668888, compound

HRID 1524649Notes

Reaction equation

HRID 1524649 reaction equation
[NH2:1][C@@:2]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])[CH2:6][O:5][C@H:4]([CH3:7])[C@H:3]1[CH:8]([OH:13])[C:9]([F:12])([F:11])[F:10].[C:21]([N:29]=[C:30]=[S:31])(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(Cl)Cl.CCOC(C)=O>[C:21]([NH:29][C:30]([NH:1][C@:2]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])[C@H:3]([CH:8]([OH:13])[C:9]([F:12])([F:10])[F:11])[C@@H:4]([CH3:7])[O:5][CH2:6]1)=[S:31])(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 2

HCID 68284Benzoyl isothiocyanateHCID 68158718HCID 68158718, compound

Product 1

HCID 86668888HCID 86668888, compoundYield 87.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

1-[(2R,3R,4S)-4-Amino-4-(2-fluoro-phenyl)-2-methyl-tetrahydro-furan-3-yl]-2,2,2-trifluoro-ethanol (Preparation Example 30-(4)) (550 mg, 1.87 mmol) was dissolved in DCM (15 mL) was transferred into the reaction vessel. Solution was cooled to 0° C. Benzoyl isothiocyanate (1.22 g, 7.50 mmol) was added drop-wise over 20 mins as a solution in DCM (100 mL). Reaction mixture was allowed to warm up to RT and stir overnight. TLC in neat EtOAc showed the weak SM spot was gone from Rf 0.10. Product was at Rf 0.40. (EtOAc:Hex 4:6), product was concentrated. Saturated aqueous sodium bicarbonate (30 ml) was added and then extracted with DCM (3×40 ml). The combined organic phases were combined and purified via flash chromatography (Hexane/EtoAc 0-50%). 0.75 g (87% yield) title compound (85%) and its epimer at the CF3 position (15%) were isolated as a brown solid. 1H NMR (400 MHz, CDCl3) ppm 1.36 (d, J=6.06 Hz, 3H) 2.66 (d, J=7.33 Hz, 1H) 4.53-4.59 (m, 1H) 4.59-4.69 (m, 2H) 4.89 (d, J=9.73 Hz, 1H) 7.05 (ddd, J=12.54, 8.18, 1.14 Hz, 1H) 7.12-7.17 (m, 1H) 7.28-7.32 (m, 1H) 7.43 (td, J=8.12, 1.58 Hz, 1H) 7.46-7.51 (m, 2H) 7.58-7.64 (m, 1H) 7.79-7.84 (m, 2H) 9.20 (s, 1H) 11.73 (s, 1H)

Workup

  1. customReaction mixture
  2. temperatureto warm up to RT
  3. concentration(EtOAc:Hex 4:6), product was concentrated
  4. additionSaturated aqueous sodium bicarbonate (30 ml) was added
  5. extractionextracted with DCM (3×40 ml)
  6. custompurified via flash chromatography (Hexane/EtoAc 0-50%)

Sources & evidence

ORD record
ord-79619ec106b54d08a457dc18c4606929
Source dataset
uspto-grants-2015_07
Patent number
US09079914B2

Reaction notes

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