Hydrochloric Acid → HCID 89463080, compound

HRID 1473261Notes

Reaction equation

HRID 1473261 reaction equation
[F:1][C:2]1[CH:35]=[CH:34][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]3[C:16]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=4)=[C:17]([CH2:22][C:23]([O:25][CH3:26])=[O:24])[N:18]([CH3:21])[C:19](=[O:20])[C:8]2=3)=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CC1(C)[C@]23C4(ON4S(=O)(=[O:54])C2)C[C@H]1CC3.Cl>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]3[C:16]([C:27]4[CH:28]=[CH:29][C:30]([CH3:33])=[CH:31][CH:32]=4)=[C:17]([CH:22]([OH:54])[C:23]([O:25][CH3:26])=[O:24])[N:18]([CH3:21])[C:19](=[O:20])[C:8]2=3)=[CH:34][CH:35]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 16212283(1R,8R)-11,11-dimethyl-5-oxa-3lambda6-thia-4-azatetracyclo[6.2.1.01,6.04,6]undecane 3,3-dioxideHCID 89463409HCID 89463409, compound

Product 1

HCID 89463080HCID 89463080, compoundYield 90.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A −78° C. solution of methyl 2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)acetate (45 mg, 0.096 mmol) in Tetrahydrofuran (THF) (1 mL) was treated with LiHMDS (0.207 mL, 0.207 mmol) and then stirred at −78° C. for 20 minutes. A solution of (1R)-(−)-(10-Camphorsulfonyl)oxaziridine (71.1 mg, 0.310 mmol) in Tetrahydrofuran (THF) (1 mL) was added and the mixture was then warmed to 0° C. for 20 minutes. The mixture was treated with HCl (1M) until pH<2 and then extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (0-100% ethyl acetate/hexanes) to afford methyl 2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)-2-hydroxyacetate (42 mg, 0.087 mmol, 90% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.30-7.45 (m, 5H) 7.16-7.26 (m, 2H) 6.89-7.02 (m, 3H) 6.54-6.63 (m, 1H) 6.29-6.37 (m, 1H) 6.13-6.24 (m, 1H) 6.01-6.11 (m, 1H) 5.34-5.42 (m, 1H) 3.81 (s, 3H) 3.70 (s, 3H) 2.51 (s, 3H); LCMS (m/z) ES+=485 (M+1).

Workup

  1. temperaturethe mixture was then warmed to 0° C. for 20 minutes
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7eb76da57c7447f6955e824e6503c760
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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