Boron Trichloride → 8-(((2S)-4-(2-thiophenylsulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-8-azabicyclo[3.2.1]octan-6-ol

HRID 1972477Notes

Reaction equation

HRID 1972477 reaction equation
C([O:8][CH:9]1[CH2:15][CH:14]2[N:16]([CH2:17][C@H:18]3[CH2:23][N:22]([S:24]([C:27]4[S:28][CH:29]=[CH:30][CH:31]=4)(=[O:26])=[O:25])[CH2:21][CH2:20][N:19]3[C:32]3[N:37]=[CH:36][C:35]([C:38]([OH:44])([CH3:43])[C:39]([F:42])([F:41])[F:40])=[CH:34][N:33]=3)[CH:10]1[CH2:11][O:12][CH2:13]2)C1C=CC=CC=1.B(Cl)(Cl)Cl>C(Cl)Cl>[S:28]1[CH:29]=[CH:30][CH:31]=[C:27]1[S:24]([N:22]1[CH2:21][CH2:20][N:19]([C:32]2[N:33]=[CH:34][C:35]([C:38]([OH:44])([CH3:43])[C:39]([F:41])([F:40])[F:42])=[CH:36][N:37]=2)[C@@H:18]([CH2:17][N:16]2[CH:10]3[CH:9]([OH:8])[CH2:15][CH:14]2[CH2:13][O:12][CH2:11]3)[CH2:23]1)(=[O:25])=[O:26]

Participants

4

Reactant 2

HCID 25135Boron TrichlorideHCID 706556422-(2-((2S)-2-((6-(benzyloxy)-3-oxa-8-azabicyclo[3.2.1]oct-8-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol

Product 1

HCID 569324268-(((2S)-4-(2-thiophenylsulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-8-azabicyclo[3.2.1]octan-6-olYield 81.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 25-mL round-bottomed flask was cooled to 0° C. and charged with 2-(2-((2S)-2-((6-(benzyloxy)-3-oxa-8-azabicyclo[3.2.1]oct-8-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol (endo) (170 mg, 0.26 mmol) and CH2Cl2 (5 mL). BCl3 (1M in CH2Cl2, 4.20 mL, 4.20 mmol) was added slowly. After 15 min at 0° C., the reaction was carefully quenched with MeOH and concentrated. The resultant foam was then recrystallized from MeOH/ether to yield an off-white solid which was purified via column chromatography (12 g silica gel, 0 to 10% MeOH in CH2Cl2) to give 8-(((2S)-4-(2-thiophenylsulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-3-oxa-8-azabicyclo[3.2.1]octan-6-ol (120 mg) (endo) as a mixture of four isomers.

Workup

  1. customthe reaction was carefully quenched with MeOH
  2. concentrationconcentrated
  3. customThe resultant foam was then recrystallized from MeOH/ether
  4. customto yield an off-white solid which
  5. customwas purified via column chromatography (12 g silica gel, 0 to 10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-91777b14cdcf4063ba6e3f91cb024e7d
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

Loading…