Hydrochloric Acid → tert-Butyl((5S,6R)-6-methyl-2-oxo-5-(o-tolyl)piperidin-3-yl)carbamate

HRID 706383Notes

Reaction equation

HRID 706383 reaction equation
C([NH2:4])(C)C.Cl.[C:6]([O:10][C:11]([NH:13][CH:14]([CH2:21][CH:22]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH3:32])[C:23](=O)[CH3:24])[C:15](OC(C)C)=[O:16])=[O:12])([CH3:9])([CH3:8])[CH3:7]>O.CS(C)=O>[CH3:24][C@H:23]1[NH:4][C:15](=[O:16])[CH:14]([NH:13][C:11](=[O:12])[O:10][C:6]([CH3:9])([CH3:8])[CH3:7])[CH2:21][C@H:22]1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH3:32]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 6363IsopropylamineHCID 89814785Tert-butyl 1-(isopropoxycarbonyl)-4-oxo-3-o-tolylpentylcarbamate

Product 1

HCID 89821824tert-Butyl((5S,6R)-6-methyl-2-oxo-5-(o-tolyl)piperidin-3-yl)carbamateYield 20,728%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of NaBO3.4H2O (10 g, 0.026 mol) in H2O (180 g) was charged isopropylamine (30 g, 0.25 mmol) dropwise at 20° C. After the mixture was stirred for 30 min, the pH was adjusted to 10.3-10.5 by 6M HCl. PLP (1 g, 6.4 mmol) and ATA-412 (25 g) was charged to the solution at 20° C. After the above mixture was stirred for 1 h, a solution of 36 (50 g, 4.7 mmoL) in DMSO (250 mL) was added slowly at 20° C. The solution was heated to 55° C. and stirred for 24 h. After the reaction was complete, the reaction was quenched by isopropyl alcohol (100 mL), and then partitioned with water and IPAc. The organic phase was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (5-20% EtOAc/PE) to give 37 (16.5 g, 40% yield). 1H (DMSO-d6, 400 MHz): δ 7.83 (s, 1H), 7.18-7.13 (m, 4H), 4.06 (br, 1H), 3.67-3.51 (m, 2H), 2.30 (d, 3H), 1.99 (t, 1H), 1.36 (s, 9H), 0.82 (m, 3H); MS (ESI) m/e [M+H]+: 319.2

Workup

  1. additionPLP (1 g, 6.4 mmol) and ATA-412 (25 g) was charged to the solution at 20° C
  2. stirringAfter the above mixture was stirred for 1 h
  3. stirringstirred for 24 h
  4. customthe reaction was quenched by isopropyl alcohol (100 mL)
  5. custompartitioned with water and IPAc
  6. dry with materialThe organic phase was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude residual was further purified by flash chromatography on silica gel (5-20% EtOAc/PE)

Sources & evidence

ORD record
ord-a778fa5f86284ae296a634d7e0990b4a
Source dataset
uspto-grants-2015_11
Patent number
US09174989B2

Reaction notes

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