Boron Trichloride → HCID 71152474, compound

HRID 1481631Notes

Reaction equation

HRID 1481631 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 131736649HCID 131736649, compound

Product 1

HCID 71152474HCID 71152474, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl ((3aR,5R,6S,7R,7aR)-6-(benzyloxy)-7-fluoro-5-((S)-1-hydroxyethyl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(methyl)carbamate (0.180 g, 0.409 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, 2.0 mL, 2.0 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-((S)-1-hydroxyethyl)-2-(methylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-6-ol as a white solid (0.092 g, 90%). 1H NMR (400 MHz, CDCl3) δ 6.45 (dd, J=1.1, 6.4 Hz, 1H), 4.59 (ddd, J=3.2, 8.1, 48.0 Hz, 1H), 4.30-4.22 (m, 1H), 4.18-4.14 (m, 1H), 4.08-4.02 (m, 1H), 3.66 (d, J=7.4 Hz, 1H), 2.83 (s, 3H), 1.22 (d, J=6.8 Hz, 3H); 13C NMR (100 MHz, CD3OD) δ 164.73, 95.14 (d, J=183.0 Hz), 92.31 (d, J=8.7 Hz), 79.15 (d, J=6.2 Hz), 69.62 (d, J=20.7 Hz), 67.98 (d, J=2.9 Hz), 67.56 (d, J=16.7 Hz), 30.28, 18.92; 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-26fea850e7fe4a57aa2fe0cf5edde497
Source dataset
uspto-grants-2016_08
Patent number
US09409924B2

Reaction notes

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