Hydrochloric Acid → (S)-2-(3,5-dichlorophenyl)morpholine

HRID 77296Notes

Reaction equation

HRID 77296 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:14][N:13](C(=O)[C@H](OC)C3C=CC=CC=3)[CH2:12][CH2:11][O:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[Li+].[B-](CC)(CC)CC.Cl>C1COCC1>[Cl:8][C:6]1[CH:5]=[C:4]([C@@H:9]2[O:10][CH2:11][CH2:12][NH:13][CH2:14]2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 23712863Lithium triethylborohydrideHCID 58049447(R)-1-((S)-2-(3,5-dichlorophenyl)-morpholino)-2-methoxy-2-phenylethanone

Product 1

HCID 26369483(S)-2-(3,5-dichlorophenyl)morpholine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Synthesized according to General Procedure 35. To a stirring solution of (R)-1-((S)-2-(3,5-dichlorophenyl)-morpholino)-2-methoxy-2-phenylethanone (24 mg, 0.06 mmol) and THF (2.2 mL), under N2, at 0° C., was added a solution of Super-hydride in THF (1.0 M, 0.4 mL, 0.4 mmol) dropwise over 10 minutes. The solution was stirred at 0° C. for 30 minutes. The solution was poured into 2M aqueous HCl solution (3 mL) and washed with diethyl ether (3×3 mL). The aqueous phase was concentrated and purified by preparative HPLC. The ee was determined to be >98%. LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=232.1; tR=1.04 min. SFC (Chiralpak IA, (0.46×25 cm), 35% methanol (0.1% DEA)/CO2, 3 mL/min): tR (S)=2.0 min, tR (R)=3.39 min.

Workup

  1. customSynthesized
  2. washwashed with diethyl ether (3×3 mL)
  3. concentrationThe aqueous phase was concentrated
  4. custompurified by preparative HPLC
  5. customtR (S)=2.0 min, tR (R)=3.39 min.

Sources & evidence

ORD record
ord-e5b31956a8854a6ea3535f4536df5097
Source dataset
uspto-grants-2014_09
Patent number
US08841282B2

Reaction notes

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