Borane → HCID 58610153, compound

HRID 1592833Notes

Reaction equation

HRID 1592833 reaction equation
B.[F:2][C:3]1[CH:4]=[C:5]([C@H:9]([OH:24])[C@H:10]2[O:15][CH2:14][CH2:13][N:12]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:11]2=O)[CH:6]=[CH:7][CH:8]=1.[F:25][C:26]1[CH:27]=[C:28]([C@@H:32]([OH:47])[C@@H:33]2[O:38][CH2:37][CH2:36][N:35]([CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:34]2=O)[CH:29]=[CH:30][CH:31]=1>O1CCCC1>[F:2][C:3]1[CH:4]=[C:5]([C@H:9]([C@@H:10]2[O:15][CH2:14][CH2:13][N:12]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:11]2)[OH:24])[CH:6]=[CH:7][CH:8]=1.[F:25][C:26]1[CH:27]=[C:28]([C@@H:32]([C@H:33]2[O:38][CH2:37][CH2:36][N:35]([CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:34]2)[OH:47])[CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 3

HCID 6331BoraneHCID 58610168HCID 58610168, compoundHCID 58610198HCID 58610198, compound

Product 2

HCID 58610153HCID 58610153, compoundHCID 58610189HCID 58610189, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of borane in tetrahydrofuran (1M, 30.7 ml) was added dropwise to a stirred solution of diastereomer 1 (2R)-2-[(S)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one and (2S)-2-[(R)-(3-fluorophenyl)(hydroxy)methyl]-4-benzylmorpholin-3-one (2.42 g 7.68 mmol) in dried tetrahydrofuran (30 ml) at room temperature under nitrogen causing effervesence. The solution was heated to 60° C. for 2 h, allowed to cool to room temperature and excess borane quenched by adding methanol (15 ml) slowly. Aqueous hydrochloric acid (1M, 15 ml) was added, heated to 60° C. for 1 h and then evaporated to a white solid. Added saturated aqueous sodium carbonate (50 ml) and diethyl ether (50 ml) to dissolve the solid and extracted with diethyl ether (2×50 ml). The extracts were washed with brine solution, dried, filtered and evaporated to a colourless oil (2.38 g). The oil was purified by chromatography on silica eluting with diethyl ether:hexane 75:25 to give (R)-[3-fluorophenyl][(2R)-4-benzylmorpholin-2-yl]methanol and (S)-[3-fluorophenyl][(2S)-4-benzylmorpholin-2-yl]methanol as a colourless oil (2.23 g)

Workup

  1. temperatureto cool to room temperature
  2. customexcess borane quenched
  3. additionby adding methanol (15 ml) slowly
  4. additionAqueous hydrochloric acid (1M, 15 ml) was added
  5. temperatureheated to 60° C. for 1 h
  6. customevaporated to a white solid
  7. dissolutionAdded saturated aqueous sodium carbonate (50 ml) and diethyl ether (50 ml) to dissolve the solid
  8. extractionextracted with diethyl ether (2×50 ml)
  9. washThe extracts were washed with brine solution
  10. customdried
  11. filtrationfiltered
  12. customevaporated to a colourless oil (2.38 g)
  13. customThe oil was purified by chromatography on silica eluting with diethyl ether:hexane 75:25

Sources & evidence

ORD record
ord-1c055c825a264ce7aac5aa4cab3e1eff
Source dataset
uspto-grants-2007_11
Patent number
US07294623B2

Reaction notes

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