Boron trifluoride → tert-butyl ((3aS,5S,6S,6aS)-6-(phenylselanyl)-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)hexahydro-2H-cyclopenta[b]furan-5-yl)carbamate

HRID 1747121Notes

Reaction equation

HRID 1747121 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.[C:33]1([Se:39]N2C(=O)C3=CC=CC=C3C2=O)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.B(F)(F)F.[OH-].[Na+]>C(Cl)Cl.O>[C:33]1([Se:39][C@@H:6]2[C@H:5]3[O:1][CH2:2][CH2:3][C@@:4]3([C:17]([N:19]3[CH2:28][CH2:27][C:26]4[N:25]=[CH:24][C:23]([C:29]([F:32])([F:31])[F:30])=[CH:22][C:21]=4[CH2:20]3)=[O:18])[CH2:8][C@@H:7]2[NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 6356Boron trifluorideHCID 14798Sodium HydroxideHCID 590397N-(Phenylseleno)phthalimideHCID 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 86708131tert-butyl ((3aS,5S,6S,6aS)-6-(phenylselanyl)-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)hexahydro-2H-cyclopenta[b]furan-5-yl)carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the product of Step D (1.51 g, 3.32 mmol, 1 eq) in DCM (40 mL) at rt under Ar was added N-(phenylseleno)phthalimide (1.60 g, 4.97 mmol, 1.5 eq) and BF3-etherate (0.042 mL, 0.33 mmol, 0.1 eq). After 2 hrs, 1 N NaOH was added and stirred 5 min., water was added, the solution extracted with DCM, the organics combined, dried over MgSO4, and concentrated. Purification by chromatography (80 g column) eluting with 50 to 100% EtOAc/heptane afforded the title compound of Step E. 1H NMR (CHLOROFORM-d) δ: 8.72 (s, 1H), 7.69 (s, 1H), 7.50-7.62 (m, 2H), 7.22-7.27 (m, 3H), 5.35 (s, 1H), 5.06 (d, J=8.1 Hz, 1H), 4.79-5.01 (m, 1H), 4.66-4.78 (m, 1H), 4.53 (br. s., 1H), 3.78-4.06 (m, 4H), 3.68-3.78 (m, 1H), 3.05-3.19 (m, 2H), 2.32 (dd, J=11.6, 5.8 Hz, 2H), 2.16 (d, J=10.9 Hz, 2H), 1.36 (s, 9H). Calculated for C28H32F3N3O4Se: 634.2 (M+23). found: 634.1.

Workup

  1. extractionthe solution extracted with DCM
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customPurification by chromatography (80 g column)
  5. washeluting with 50 to 100% EtOAc/heptane

Sources & evidence

ORD record
ord-cebd135c09b4427abcfad7b4378a13b5
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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