Boron Trichloride → HCID 71152537, compound

HRID 1481627Notes

Reaction equation

HRID 1481627 reaction equation
C([O:8][C@@H:9]1[C@@H:17]([C@:18]([OH:24])([CH3:23])[C:19]([F:22])([F:21])[F:20])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:25](C)[C:26](=O)OC(C)(C)C)[S:14]2)[C@@H:10]1[F:34])C1C=CC=CC=1.[Si](C(F)(F)F)(C)(C)C.B(Cl)(Cl)Cl>C(Cl)Cl>[F:34][C@H:10]1[C@H:11]2[N:12]=[C:13]([NH:25][CH3:26])[S:14][C@H:15]2[O:16][C@H:17]([C@:18]([OH:24])([CH3:23])[C:19]([F:22])([F:21])[F:20])[C@H:9]1[OH:8]

Participants

5

Reactant 3

HCID 25135Boron TrichlorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 131736646HCID 131736646, compound

Product 1

HCID 71152537HCID 71152537, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl ((3aR,5S,6R,7S,7aR)-6-(benzyloxy)-7-fluoro-5-((R)-1,1,1-trifluoro-2-hydroxypropan-2-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (major isomer from the TMSCF3 addition step) (0.18 g, 0.35 mmol) and PMB (0.15 g, 1.0 mmol) in dry DCM (5 mL) at −78° C. under N2, was added BCl3 (1.0 M in DCM, 2.0 mL, 2.0 mmol). The mixture was stirred for ˜4 h while the temperature of the cooling bath slowly warmed to room temperature. The reaction mixture was cooled at −78° C., quenched with mixed MeOH/DCM, and then concentrated to dryness. The residue was purified on silica gel by flash column chromatography (1.0 M NH3 in MeOH/DCM, 1:13), affording (3aR,5S,6R,7S,7aR)-7-fluoro-2-(methylamino)-5-((R)-1,1,1-trifluoro-2-hydroxypropan-2-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-6-ol as a white solid (0.086 g, 77%). 1H NMR (600 MHz, CD3OD) δ 6.37 (d, J=6.7 Hz, 1H), 4.83 (ddd, J=3.5, 4.6, 46.7 Hz, 1H), 4.61-4.57 (m, 1H), 4.33-4.30 (m, 1H), 3.90 (d, J=6.9 Hz), 2.88 (s, 3H), 1.34 (s, 3H); 13C NMR (150.9 MHz, CD3OD) δ 165.55, 127.29 (q, J=286.0 Hz), 90.86 (d, J=8.4 Hz), 89.66 (d, J=186.5 Hz), 76.23 (d, J=4.0 Hz), 75.41 (q, J=27.4 Hz), 72.65 (d, J=16.6 Hz), 67.79 (d, J=16.6 Hz), 30.84, 17.28; MS, (ES, m/z) [M+H]+ 319.1.

Workup

  1. temperatureThe reaction mixture was cooled at −78° C.
  2. customquenched with mixed MeOH/DCM
  3. concentrationconcentrated to dryness
  4. customThe residue was purified on silica gel by flash column chromatography (1.0 M NH3 in MeOH/DCM, 1:13)

Sources & evidence

ORD record
ord-83f5d672f3b24d47a946597f9a19af47
Source dataset
uspto-grants-2016_08
Patent number
US09409924B2

Reaction notes

Loading…