Trifluoroacetic acid → 2-methylpropyl[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]carbamate

HRID 1979067Notes

Reaction equation

HRID 1979067 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:15][C:16](=[O:22])[O:17][CH2:18][CH:19]([CH3:21])[CH3:20])[CH:5]=[CH:6][C:7]=1[C:8]1(O)[CH2:13][CH2:12][S:11][CH2:10][CH2:9]1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:20][CH:19]([CH3:21])[CH2:18][O:17][C:16](=[O:22])[NH:15][C:4]1[CH:5]=[CH:6][C:7]([C:8]2[CH2:13][CH2:12][S:11][CH2:10][CH:9]=2)=[C:2]([F:1])[CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 98403602-methylpropyl [3-fluoro-4-(tetrahydro-4-hydroxy-2H-thiopyran-4-yl)phenyl]carbamate

Product 1

HCID 155500492-methylpropyl[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Methylpropyl [3-fluoro-4-(tetrahydro-4-hydroxy-2H-thiopyran-4-yl)phenyl]carbamate (IV, EXAMPLE 2, 50 g, 152.7 mmol) is slurried in 150 ml methylene chloride. Trifluoroacetic acid (21.1 ml, 274.9 mmol, 1.8 equiv.) is added and the resulting mixture is stirred at 25° for 3 hr. The reaction is quenched with 75 ml of 47% aqueous potassium carbonate and stirred at 25° for 2 hr to dissolve any salts. Water (75 ml) is added and the phases are separated. The organic layer is collected, washed with 75 ml saline followed by 75 ml water. The organic phase is then concentrated and dried under reduced pressure over night to give 2-methylpropyl[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]carbamate. TLC Rf=0.85 (methanol/methylene chloride, 5/95); mp=99-100°; NMR (CDCl3) d 7.28, 7.12, 6.99, 6.74, 5.99, 3.95, 3.33-3., 2.84, 2.63, 2.02-1.91 and 0.96; CMR (CDCl3) d 159.5, 153.4, 138.4, 134.5, 129.6, 126.8, 124.0, 113.8, 106.2, 71.5, 29.3, 27.9, 25.8, 25.1 and 18.9; MS (CI, NH3) m/z (relative intensity) 327 (80), 310 (100), 309(87), 281 (23), 264 (38), 235 (30), 224(33), 189 (20), 165(25) and 161 (23).

Workup

  1. customThe reaction is quenched with 75 ml of 47% aqueous potassium carbonate
  2. stirringstirred at 25° for 2 hr
  3. dissolutionto dissolve any salts
  4. additionWater (75 ml) is added
  5. customthe phases are separated
  6. customThe organic layer is collected
  7. washwashed with 75 ml saline
  8. concentrationThe organic phase is then concentrated
  9. customdried under reduced pressure over night

Sources & evidence

ORD record
ord-e64a0efad18b4e158d83233e0c1c53de
Source dataset
uspto-grants-2001_05
Patent number
US06239283B1

Reaction notes

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