Boron Trichloride → HCID 71152194, compound

HRID 1497284Notes

Reaction equation

HRID 1497284 reaction equation
[N:1]1([C:5]2[O:6][C@H:7]3[CH2:13][C@H:12]([CH2:14][F:15])[C@@H:11]([O:16]CC4C=CC=CC=4)[C@H:10]([O:24]CC4C=CC=CC=4)[C@H:8]3[N:9]=2)[CH2:4][CH2:3][CH2:2]1.B(Cl)(Cl)Cl.CO.C(Cl)Cl>C(Cl)Cl>[N:1]1([C:5]2[O:6][C@H:7]3[CH2:13][C@H:12]([CH2:14][F:15])[C@@H:11]([OH:16])[C@H:10]([OH:24])[C@H:8]3[N:9]=2)[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 25135Boron TrichlorideHCID 21226129Dichloromethane methanolHCID 117856674HCID 117856674, compound

Product 1

HCID 71152194HCID 71152194, compoundYield 79.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (3aS,4R,5R,6S,7aS)-2-(azetidin-1-yl)-4,5-bis(benzyloxy)-6-(fluoromethyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole (80.0 mg, 0.189 mmol) in DCM (2 mL) at −78° C. was added a solution of BCl3 in DCM (1.0 M, 0.47 mL, 0.47 mmol). The mixture was slowly warmed up to 0° C. and stirred at this temperature for 5 h. The reaction was cooled to −78° C. again and a 1:1 mixture of MeOH-DCM (5 mL) was added dropwise to quench the reaction. Solvents were evaporated and the residue was treated with MeOH for three more times. The crude product was purified by silica gel column chromatography, eluted with 3%-8% 2 M NH3 MeOH solution in DCM to give the product (3aR,4R,5R,6S,7aS)-2-(azetidin-1-yl)-6-(fluoromethyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole-4,5-diol (36.5 mg, 79%) as a white solid. MS m/z 267.2 (M+23, 100%); 1H NMR (400 MHz, MeOD) δ 4.61-4.69 (m, 1.5H), 4.53-4.57 (m, 1H), 4.43 (dd, J=9.0 Hz, 2.8 Hz, 1H), 4.00 (t, J=7.6 Hz, 1H), 3.58 (t, J=7.2 Hz, 1H), 3.15-3.28 (m, 2H), 2.22-2.36 (m, 3H), 1.75-1.87 (m, 2H); 13C NMR (100 MHz, MeOD) δ 164.81, 85.13 (d, J=160.7 Hz), 81.98, 80.60 (d, J=0.6 Hz), 71.88 (d, J=4.8 Hz), 69.03, 39.37 (d, J=18.6 Hz), 28.09 (d, J=3.9 Hz), 17.75.

Workup

  1. temperatureThe reaction was cooled to −78° C. again
  2. additionwas added dropwise
  3. customto quench
  4. customthe reaction
  5. customSolvents were evaporated
  6. additionthe residue was treated with MeOH for three more times
  7. customThe crude product was purified by silica gel column chromatography
  8. washeluted with 3%-8% 2 M NH3 MeOH solution in DCM

Sources & evidence

ORD record
ord-33dc111fee604540aac29e0e4d5e45c4
Source dataset
uspto-grants-2015_12
Patent number
US09199949B2

Reaction notes

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