Hydrochloric Acid → (3R,4S)-1-(4-Fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-[4-(phenylmethoxy)phenyl]-2-azetidinone

HRID 341903Notes

Reaction equation

CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.[F:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]2[C@H:32]([C:33]3[CH:38]=[CH:37][C:36]([O:39][CH2:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[CH:35][CH:34]=3)[C@@H:31]([CH2:47][CH2:48][C:49]([C:51]3[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=3)=[O:50])[C:30]2=[O:58])=[CH:25][CH:24]=1.[BH4-].CSC.Cl>C1COCC1.CO>[F:22][C:23]1[CH:24]=[CH:25][C:26]([N:29]2[C@H:32]([C:33]3[CH:34]=[CH:35][C:36]([O:39][CH2:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[CH:37][CH:38]=3)[C@@H:31]([CH2:47][CH2:48][C@@H:49]([C:51]3[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=3)[OH:50])[C:30]2=[O:58])=[CH:27][CH:28]=1

Participants

Conditions

Temperature: -20 °C

Procedure

Add (R)-tetrahydro-1-methyl-3,3-diphenyl-1H,3H-pyrrolo[1,2-c]-[1,3,2]oxazaborole (120 mg, 0.43 mmol) to 1-(4-fluorophenyl)-3(R)-(3-(4-fluorophenyl)-3-oxopropyl)-4(S)-(4-benzyloxyphenyl)-2-azetidinone (0.95 g, 1.91 mmol) in THF (3 mL) and cool to -20° C. After 5 min., add borohydride-dimethylsulfide complex (2M in THF, 0.85 mL, 1.7 mmol) dropwise over 0.5 h. After a total of 1.5 h, add CH3OH followed by HCl (1N) and extract the reaction mixture with EtOAc to obtain 1-(4-fluorophenyl)-3(R)-(3(S)-(4-fluorophenyl)-3-hydroxypropyl)-4(S)-(4-benzyloxyphenyl)-2-azetidinone.

Workup

extractionextract the reaction mixture with EtOAc

Sources & evidence

ORD record: ord-1f13f27e3597424995b6dff231048107
Source dataset: uspto-grants-1999_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05856473

Reaction notes

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