Ammonium Chloride → HCID 68646427, compound

HRID 1162641Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=O)[C@@H:10]([NH:14][C:15]([C:17]2[S:18][C:19]([Cl:22])=[CH:20][CH:21]=2)=[O:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl-].[NH4+].CC[N:27](C(C)C)C(C)C.[BH4-].[Na+]>CCO.CCOC(C)=O.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4]>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]([NH:14][C:15]([C:17]2[S:18][C:19]([Cl:22])=[CH:20][CH:21]=2)=[O:16])[C@@H:11]([NH2:27])[CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 40 °C

Procedure

35.2 A solution of 500 mg (S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester in 20 ml EtOH was treated with 155 mg ammonium chloride, 0.49 ml Hünig's base and 0.86 ml tetraisopropyl orthotitanate. The reaction mixture was stirred for 5 hrs at 40° C. Then it was cooled to 0° C., treated with 110 mg NaBH4 and stirred at r.t. overnight. The mixture was diluted with EtOAc and washed with H2O. The organic layer was dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel, gradient: CH2Cl2->CH2Cl2/MeOH 9:1) to give 180 mg (S)-3-amino-4-[(5-chloro-thiophene-2-carbonyl)-amino]-pyrrolidine-1-carboxylic acid tert-butyl ester as yellow solid. MS 344.3 ([M−H]−)

Workup

temperatureThen it was cooled to 0° C.
stirringstirred at r.t. overnight
washwashed with H2O
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by column chromatography (silica gel, gradient: CH2Cl2->CH2Cl2/MeOH 9:1)

Sources & evidence

ORD record: ord-a906de0c652b4c3ab6b3062fe3a28279
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07820699B2

Reaction notes

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