Triphenylphosphine → N-(7a-(5-bromo-2-fluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

HRID 2060753Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C:8]2([NH:15][C:16]([NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[S:17])[CH:12]([CH2:13]O)[CH2:11][O:10][CH2:9]2)[CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C:8]23[CH2:9][O:10][CH2:11][CH:12]2[CH2:13][S:17][C:16]([NH:18][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:15]3)[CH:7]=1

Participants

Conditions

Temperature: 25 °C

Procedure

To a 15° C. mixture of racemic N-((3SR,4RS)-3-(5-bromo-2-fluorophenyl)-4-(hydroxymethyl)tetrahydrofuran-3-ylcarbamothioyl)benzamide (110 g, 243 mmol) and triphenylphosphine (76.4 g, 291 mmol) in tetrahydrofuran (970 mL) is added di-tert-butyl azodicarboxylate (67.1 g, 291 mmol) in 3 portions over 10 minutes keeping internal temperature below 25° C. After the addition, the reaction mixture is stirred at 25° C. for 1 hour. The solvent is removed under reduced pressure and the residue is purified by silica gel chromatography using a linear gradient of 14% to 33% ethyl acetate in hexanes to give the title compound (80 g, 76%). ES/MS m/e (79Br/81Br) 435, 437 (M+1).

Workup

customtemperature below 25° C
additionAfter the addition
customThe solvent is removed under reduced pressure
customthe residue is purified by silica gel chromatography

Sources & evidence

ORD record: ord-fdddfca01db94ba3b0bf5e68a55560a4
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278441B2

Reaction notes

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