Triphenylphosphine → tert-butyl (3S,9aS)-3-(3-cyano-4-fluoro-2-methylphenyl)hexahydropyrazino[2,1-c][1,4]thiazine-8(1H)-carboxylate 2,2-dioxide

HRID 1502008Notes

Reaction equation

[C:1]([C:3]1[C:4]([CH3:30])=[C:5]([C@@H:10]2[S:15](=[O:17])(=[O:16])[CH2:14][C@@H:13]3[CH2:18][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:20][CH2:21][N+:12]3([O-])[CH2:11]2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.CO>[C:1]([C:3]1[C:4]([CH3:30])=[C:5]([C@@H:10]2[S:15](=[O:16])(=[O:17])[CH2:14][C@@H:13]3[CH2:18][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:20][CH2:21][N:12]3[CH2:11]2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2]

Participants

Conditions

Temperature: 80 °C

Procedure

The above compound from step A (23 mg, 0.052 mmol) was combined with TRIPHENYLPHOSPHINE (24.71 mg, 0.094 mmol) in DMF (0.4 M) and warmed to 80° C. for 20 minutes. LC-Ms showed the completion of the reaction. The reaction mixture was diluted with methanol and purified with mass-directed reverse phase HPLC eluting with 10% acetonitrile/water with 0.1% TFA to 100% acetonitrile with 0.1% TFA to yield the title compound: 1H-NMR (500 MHz, CD3OD): δ ppm 9.05 (m, 1H), 7.24 (m, 1H), 4.63 (bs, 1H), 4.03 (m, 2H), 3.32-3.45 (m, 2H), 3.05 (m, 3H), 2.92 (m, 1H), 2.75 (m, 2H), 2.63 (S, 3H), 2.25 (m, 1H), 1.48 (s, 9H); LC-MS: M+1=424.

Workup

customthe completion of the reaction
custompurified with mass-directed reverse phase HPLC
washeluting with 10% acetonitrile/water with 0.1% TFA to 100% acetonitrile with 0.1% TFA

Sources & evidence

ORD record: ord-311d55a00539419ca97107d5f6977762
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206199B2

Reaction notes

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