Boron Trichloride → HCID 71152363, compound

HRID 1481630Notes

Reaction equation

HRID 1481630 reaction equation
C([O:8][C@H:9]1[C@@H:17]([C@H:18]([OH:20])[CH3:19])[O:16][C@H:15]2[C@H:11]([N:12]=[C:13]([N:21](C)[C:22](=O)OC(C)(C)C)[S:14]2)[C@H:10]1[F:30])C1C=CC=CC=1.B(Cl)(Cl)Cl>C(Cl)Cl>[F:30][C@@H:10]1[C@H:11]2[N:12]=[C:13]([NH:21][CH3:22])[S:14][C@H:15]2[O:16][C@H:17]([C@H:18]([OH:20])[CH3:19])[C@@H:9]1[OH:8]

Participants

4

Reactant 2

HCID 25135Boron TrichlorideHCID 131736648HCID 131736648, compound

Product 1

HCID 71152363HCID 71152363, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl ((3aR,5R,6S,7R,7aR)-6-(benzyloxy)-7-fluoro-5-((R)-1-hydroxyethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (0.116 g, 0.264 mmol) and PMB (0.20 g, 1.3 mmol) in anhydrous DCM (6 mL) at −78° C. under N2, was added BCl3 (1.0 M in DCM, 1.2 mL, 1.2 mmol). The mixture was stirred for ˜3 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, 1:10), affording (3aR,5R,6S,7R,7aR)-7-fluoro-5-((R)-1-hydroxyethyl)-2-(methylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-6-ol as a white solid (0.064 g, 97%). 1H NMR (400 MHz, CDCl3) δ 6.43 (dd, J=1.4, 6.5 Hz, 1H), 4.51 (ddd, J=3.2, 8.2, 48.2 Hz, 1H), 4.35-4.32 (m, 1H), 4.30-4.22 (m, 1H), 4.03-3.96 (m, 1H), 3.57 (d, J=8.2 Hz, 1H), 2.86 (s, 3H), 1.20 (d, J=6.3 Hz, 3H); 13C NMR (100 MHz, CD3OD) δ 164.40, 95.50 (d, J=183.3 Hz), 92.85 (d, J=8.6 Hz), 78.33 (d, J=6.2 Hz), 69.39 (d, J=20.8 Hz), 66.14 (d, J=16.5 Hz), 65.95 (d, J=8.4 Hz), 30.23, 20.71; MS, (ES, m/z) [M+H]+ 251.1.

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, 1:10)

Sources & evidence

ORD record
ord-a8d4b793046b4120913bde14d256c59d
Source dataset
uspto-grants-2016_08
Patent number
US09409924B2

Reaction notes

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