Sodium Thiosulfate → tert-butyl ((1S,4S)-4-(2-oxoethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

HRID 1747126Notes

Reaction equation

HRID 1747126 reaction equation
[OH:1][CH2:2][CH2:3][C@@:4]1([C:17]([N:19]2[CH2:28][CH2:27][C:26]3[N:25]=[CH:24][C:23]([C:29]([F:32])([F:31])[F:30])=[CH:22][C:21]=3[CH2:20]2)=[O:18])[CH2:8][C@H:7]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:6]=[CH:5]1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl>[O:1]=[CH:2][CH2:3][C@@:4]1([C:17]([N:19]2[CH2:28][CH2:27][C:26]3[N:25]=[CH:24][C:23]([C:29]([F:32])([F:31])[F:30])=[CH:22][C:21]=3[CH2:20]2)=[O:18])[CH2:8][C@H:7]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:6]=[CH:5]1

Participants

6

Reactant 4

HCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 516892Sodium BicarbonateHCID 86708129tert-butyl ((1S,4S)-4-(2-hydroxyethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

Product 1

HCID 86708134tert-butyl ((1S,4S)-4-(2-oxoethyl)-4-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)cyclopent-2-en-1-yl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product of Example 1, Step D (417 mg, 0.92 mmol, 1 eq) in DCM (20 mL) at 0° C. was added Dess-Martin periodinane (427 mg, 1.01 mmol, 1.1 eq). After 1 hr, saturated sodium bicarbonate and sodium thiosulfate were added, after 10 minutes, the aqueous was extracted with DCM, the organics combined, dried over MgSO4 and concentrated. Purification by chromatography (12 g column) eluting with 30 to 60% EtOAc/heptane afforded the title compound of Step A. 1H NMR (CHLOROFORM-d) δ: 9.74 (s, 1H), 8.70 (s, 1H), 7.72 (s, 1H), 6.31 (dd, J=5.6, 1.7 Hz, 1H), 5.91 (dd, J=5.6, 1.5 Hz, 1H), 5.01 (d, J=17.1 Hz, 1H), 4.65-4.87 (m, 3H), 4.07-4.21 (m, 1H), 3.79-3.95 (m, 1H), 3.10 (q, J=5.6 Hz, 2H), 3.03 (d, J=16.6 Hz, 1H), 2.63 (dd, J=13.6, 7.2 Hz, 1H), 2.52 (dd, J=16.6, 1.5 Hz, 1H), 2.11 (dd, J=13.1, 7.7 Hz, 1H), 1.44 (s, 9H). Calculated for C22H26F3N3O4: 454.2 (M+1). found: 454.2.

Workup

  1. extractionthe aqueous was extracted with DCM
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customPurification by chromatography (12 g column)
  5. washeluting with 30 to 60% EtOAc/heptane

Sources & evidence

ORD record
ord-a4ba6252c0bf485aa3df2df2418a0f48
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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