Tetrahydrofuran → (S)-tert-butyl 3-(amino(3-chloro-4-fluorophenyl)methyl)pyrrolidine-1-carboxylate

HRID 715065Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([N:22]2C(=O)C3C(=CC=CC=3)C2=O)[C@H:10]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11]2)[CH:5]=[CH:6][C:7]=1[F:8].C1COCC1.O.NN>CO>[NH2:22][CH:9]([C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Cl:1])[CH:3]=1)[C@H:10]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11]1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of 71a/71b (212.3 mg, 0.4626 mmol) in 1:1 THF:MeOH (2.3 mL, 0.2 M) was treated with hydrazine monohydrate (224.4 μL, 4.626 mmol) and heated to 60° C. overnight. The reaction was cooled to RT, and the solids were filtered off. The filtrate was concentrated to dryness and taken up in EtOAc (30 mL). The EtOAc solution was washed with saturated NaHCO3 (2×30 mL) and brine (1×30 mL). The organics were isolated, dried (Na2SO4), filtered and concentrated. The crude product was purified by SiO2 chromatography eluting with a 1-25% gradient of MeOH/3% NH4OH in DCM to afford 110 mg (72%) of 73a/73b as a clear oil containing approximately a 1:1 mixture of diastereomers.

Workup

temperatureThe reaction was cooled to RT
filtrationthe solids were filtered off
concentrationThe filtrate was concentrated to dryness
washThe EtOAc solution was washed with saturated NaHCO3 (2×30 mL) and brine (1×30 mL)
customThe organics were isolated
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by SiO2 chromatography
washeluting with a 1-25% gradient of MeOH/3% NH4OH in DCM

Sources & evidence

ORD record: ord-2b898ce841f1480b99037f9f151d004a
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187462B2

Reaction notes

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