Boron Trichloride → HCID 71152255, compound

HRID 1497282Notes

Reaction equation

HRID 1497282 reaction equation
C([O:8][C@@H:9]1[C@H:14]2[N:15]=[C:16]([NH:18][CH2:19][CH3:20])[O:17][C@H:13]2[CH2:12][C@H:11]([CH2:21][F:22])[C@H:10]1[O:23]CC1C=CC=CC=1)C1C=CC=CC=1.B(Cl)(Cl)Cl.CO.C(Cl)Cl>C(Cl)Cl>[CH2:19]([NH:18][C:16]1[O:17][C@H:13]2[CH2:12][C@H:11]([CH2:21][F:22])[C@@H:10]([OH:23])[C@H:9]([OH:8])[C@H:14]2[N:15]=1)[CH3:20]

Participants

5

Reactant 3

HCID 25135Boron TrichlorideHCID 21226129Dichloromethane methanolHCID 71152529HCID 71152529, compound

Product 1

HCID 71152255HCID 71152255, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (3aS,4R,5R,6S,7aS)-4,5-bis(benzyloxy)-N-ethyl-6-(fluoromethyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazol-2-amine (209 mg, 0.507 mmol) in DCM (5 mL) at −78° C. was added a solution of BCl3 in DCM (1.0 M, 1.27 mL, 1.27 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 (10 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 5%-15% 2 M NH3 MeOH solution in DCM to give the product (3aR,4R,5R,6S,7aS)-2-(ethylamino)-6-(fluoromethyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole-4,5-diol (86.0 mg, 73%) as a white solid. MS m/z 233.2 (M+1, 100%); 1H NMR (400 MHz, MeOD) δ 4.60 (dd, J=9.0 Hz, 4.4 Hz, 0.5H), 4.45-4.51 (m, 2H), 4.35 (dd, J=9.0 Hz, 2.5 Hz, 0.5H), 3.47 (t, J=7.1 Hz, 1H), 3.13-3.22 (m, 2H), 3.06-3.12 (m, 2H), 2.12-2.21 (m, 1H), 1.65-1.80 (m, 2H), 1.06 (t, J=7.3 Hz, 3H); 13C NMR (100 MHz, MeOD) δ 163.88, 84.63 (d, J=165.6 Hz), 80.81, 80.65, 71.86 (d, J=4.8 Hz), 68.43, 39.40 (d, J=18.6 Hz), 38.23 (d, J=2.4 Hz), 28.14 (d, J=3.8 Hz), 15.24.

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 5%-15% 2 M NH3 MeOH solution in DCM

Sources & evidence

ORD record
ord-27653207815d413ba8cae1a26236c593
Source dataset
uspto-grants-2015_12
Patent number
US09199949B2

Reaction notes

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